PPARa基因和apM1基因多态性与冠心病和2型糖尿病相关性研究
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摘要
目的:流行病学研究表明,脂代谢紊乱是冠心病(coronary heart disease, CHD)的危险因素,也可能影响个体对2型糖尿病( type 2 diabetes mellitus, T2DM)即非胰岛素依赖型糖尿病( non-insulin-dependent diabetes mellitus,NIDDM)易感性。过氧化物酶体增殖物激活受体和脂联素均与脂代谢有关。因此,本研究的目的在于探讨影响血脂代谢过程的脂代谢相关基因―过氧化物酶体增殖物激活型受体( PPARa)基因和脂联素( apM1)基因单核苷酸多态性(single nucleotide polymorphism, SNP)与四川地区汉族人群CHD及T2DM的相关性及两者基因相互作用对CHD及T2DM的影响。这些SNP为PPARa基因-12601A>C、PPARa基因-20337A>G、apM1基因-3971G>A、apM1基因+4544C>G。
方法:以369例CHD患者、401例T2DM患者、339例正常对照为研究对象,采用PCR-RFLP技术对PPARa基因-12601A>C、PPARa基因-20337A>G、apM1基因-3971G>A、apM1基因+4544C>G多态位点的基因型和等位基因频率分布,应用SPSS 12.0软件对四种基因多态的不同基因型与血脂水平进行比较、PPARa基因两多态位点各亚型中apM1基因各亚型在CHD、T2DM及正常对照组中的分布进行分析。
结果:1.PPARa基因-12601A>C多态性: CHD组、T2DM组和对照组之间基因型分布及等位基因频率无显著性差别(P均>0.05)。CHD组中的A/A纯合子的TG值显著低于C/C纯合子(A/AVSC/C,q=3.9644,P<0.05), A/A纯合子的TC值显著低于A/C杂合子和C/C纯合子(A/AVSA/C,q=7.88,P<0.01;A/AVSC/C,q=4.2867,P<0.01)。T2DM组中的A/A纯合子的TG值显著低于A/C杂合子和C/C纯合子(A/AVSA/C,q=3.1570,P<0.05;A/AVSC/C,q=4.2867,P<0.01)。
2. PPARa基因-20337A>G多态性: CHD组、T2DM组与对照组之间基因型分布及等位基因频率无显著性差别(P均>0.05)。CHD组中A/A纯合子的TG值显著低于A/G杂合子和G/G纯合子(A/AVSA/G,q=4.5245,P<0.01;A/AVSG/G,q=5.2867,P<0.01)。T2DM组中的A/A纯合子的TG值低于A/G杂合子和G/G纯合子(A/AVSA/G,q=3.6986,P<0.05;A/AVSG/G,q=2.9384,P<0.05)及A/A纯合子的HDL-C值高于A/G杂合子和G/G纯合子(A/AVSA/G,q=3.157,P<0.05;A/AVSG/G, q=3.7857,P<0.05)。正常对照组中的A/G杂合子的TC值显著高于G/G纯合子(A/GVSG/G,q=3.5954,P<0.05)。
3.apM1基因-3971A>G多态性: CHD组、T2DM组与对照组之间基因型分布及等位基因频率无显著性差别(P均>0.05)。CHD组中A/A纯合子的TG值显著低于A/G杂合子和G/G纯合子(A/AVSA/G,q=3.9644,P<0.05 ;A/AVSG/G,q=4.2867,P<0.01), A/A纯合子的LDL-C值低于A/G杂合子和G/G纯合子(A/AVSA/G,q=7.88,P<0.01;A/AVSG/G, q=4.2867,P<0.01)。T2DM组中A/A纯合子的TG值低于A/G杂合子和G/G纯合子(A/AVSA/G,q=3.5242,P<0.05 ;A/AVSG/G,q=3.5813,P<0.05)。
4. apM1基因+4544C>G多态性: CHD组、T2DM组和对照组之间基因型分布无显著性差别(P均>0.05)。apM1基因+4544C>G多态的等位基因频率分布在T2DM患者和正常对照中没差别,因此可认为apM1基因+4544C>G多态性与T2DM无相关性。在CHD组中apM1基因+4544C稀有等位基因频率高于对照组并有显著性的差别,因此可认为apM1基因+4544C>G多态性与CHD存在相关性。CHD组中C/C纯合子的TG值显著低于C/G杂合子和G/G纯合子(C/CVSC/G,q=7.1224,P<0.01 ;C/CVSG/G,q=3.5441,P<0.05), C/C纯合子的LDL-C值显著低于C/G杂合子和G/G纯合子(C/CVSC/G,q=3.6986,P<0.05;C/CVSC/G,q=2.9384,P<0.05)。对照组中的G/G纯合子的TG值显著高于C/C纯合子和C/G杂合子(G/GVSC/C,q=3.4038,P<0.05; G/GVSC/G,q=4.3349,P<0.01)。
5. PPARa基因的-12601A>C多态性AC亚型中apM1基因-3971A>G基因型在T2DM组与正常对照组分布有显著性的差别(x2=11.2, P<0.05)。PPARa基因的-12601A>C多态性CC亚型中apM1基因-3971A>G的各亚型在T2DM组与正常对照组中分布不同(x2=11.2, P<0.05)。PPARa基因的-12601A>C多态性AC亚型中apM1基因+4544C>G的各亚型在CHD组和T2DM组与正常对照组分布不同(x2=20.9, P<0.05; x2=12.5, P<0.05)。
PPARa基因的-20337A>G多态性GG亚型中apM1基因-3971A>G的各亚型在CHD组与正常对照组中的分布不同(x2=6.18, P<0.05)。PPARa基因的-20337A>G多态性AA亚型中apM1基因+4544C>G的各亚型在CHD组与正常对照组中的分布不同(x2=13.4, P<0.05)。PPARa-20337AG基因亚型中apM1+4544C>G基因型在CHD组、T2DM组与正常对照组分布不同(x2=16.6,P<0.05; x2=7.65,P<0.05)。
结论:上述结果表明,PPARa基因-12601A>C多态性、PPARa基因的-20337A>G多态性、apM1基因-3971A>G多态性及apM1基因+4544C>G多态性与T2DM不存在相关性。PPARa-12601A>C多态性、PPARa基因的-20337A>G多态性、apM1基因-3971A>G多态性与CHD不存在相关性,但apM1基因+4544C>G多态性与CHD存在相关性。PPARa基因-12601A>C多态性与CHD和T2DM中的血脂有关,PPARa基因的-20337A>G多态性与T2DM中的血脂有关,apM1基因-3971A>G多态性与CHD和T2DM的血脂有关,apM1基因+4544C>G多态性与CHD的血脂有关。PPARa基因多态性与apM1基因多态性协同作用对CHD和T2DM有影响。
Objective: Many epidemiological studies and reviews have demonstrated that dyslipidemia was associated with heterogeneity of the onset and severity of coronary heart disease (CHD), in addition, it is also a clinical feature of type 2 diabetes mellitus (T2DM), and then it has been proposed to be a risk factor for T2DM. The purpose of this study was to evaluate the influence of variants in the lipid metabolism related genes peroxisome proliferators-activated receptor-a(PPARa)、apM1 on the risk of developing CHD and T2DM and the effect between the two genes interaction CHD and T2DM. These variants were -12601A>C and -20337A>G polymorphisms in the PPARa gene,-3971 A>G and +4544 C>G polymorphisms in apM1 gene.
Methods: We examined these four single nucleotide polymorphisms (SNPs)( -12601A>C and -20337A>G polymorphisms in the PPARa gene, -3971A>G and C4544G polymorphisms in the apM1 gene) in 369 patients with CHD,401 patients with T2DM and in 339 controls by PCR-RFLP. Then,we analysed the association of these SNPs with lipid metabolism in patients with CHD、T2DM and controls. Case-control comparisons were performed separately for CHD、T2DM and controls by using SPSS statistical software package.
Results: 1.No significant difference of allelic or genotypic frequencies either of -12601A>C polymorphism in PPARa gene between the CHD、T2DM patient and control subjects were observed.The value of TG in homozygous A/A of the CHD is lower in homozygous C/C of the CHD(A/AVSA/C,q=3.9644,P<0.05). The value of TC in homozygous A/A of the CHD is lower in heterozygote A/C of the CHD and in homozygous C/C of the CHD(A/AVSA/C,q=7.88,P<0.01;A/AVSC/C,q=4.2867,P<0.01) . The value of TG in homozygous A/A of the T2DM is lower in heterozygote A/C of the CHD and in homozygous C/C of the (A/AVSA/C,q=3.1570,P<0.05;A/AVSC/C,q=4.2867,P<0.01)
2. No significant difference of allelic or genotypic frequencies either of -20337A>G polymorphism in PPARa gene between the CHD, T2DM patient and control subjects were observed.The value of TG in homozygous A/A of the CHD is lower in heterozygote A/G of the CHD and in homozygous G/G of the CHD (A/AVSA/G,q=4.5245,P<0.01;A/AVSG/G,q=5.2867,P<0.01). The value of TG in homozygous A/A of the T2DM is lower in heterozygote A/G of the T2DM and in homozygous G/G of the CHD (A/AVSA/G,q=3.6986,P<0.05;A/AVSG/G,q=2.9384,P<0.05). The value of HDL-C in homozygous A/A of theT2DM is higher in heterozygote A/C of the T2DM and in homozygous G/G of the T2DM ((A/AVSA/G,q=3.157,P<0.05;A/AVSG/G,q=3.7857,P<0.05)) . The value of TG in heterozygote A/G of the controls is higher in homozygous G/G of the controls (A/GVSG/G,q=3.5954,P<0.05).
3.No significant difference of allelic or genotypic frequencies either of -3971A>G polymorphism in apM1 gene between the CHD, T2DM patient and control subjects were observed.The value of TG in homozygous A/A of the CHD is lower in heterozygote A/G of the CHD and in homozygous G/G of the CHD (A/AVSA/G,q=3.9644,P<0.05 ;A/AVSG/G,q=4.2867,P<0.01). The value of LDL-C in homozygous A/A of the CHD is lower in heterozygote A/G of the CHD and in homozygous G/G of the CHD ((A/AVSA/G,q=7.88,P<0.01;A/AVSG/G,q=4.2867,P<0.01)。The value of TG in homozygous A/A of the T2DM is higher in heterozygote A/C of the CHD and in homozygous G/G of the T2DM (A/AVSA/G,q=3.5242,P<0.05 ;A/AVSG/G,q=3.5813,P<0.05).
4. No significant difference of allelic or genotypic frequencies either of +4544C>G polymorphism in apM1 gene between the CHD patient and control subjects were observed. No significant difference of genotypic frequencies either of +4544C>G polymorphism in apM1 gene between the T2DM patient and control subjects were observed.There is significant difference of allelic frequencies either of +4544C>G polymorphism in apM1 gene between the T2DM patient and control subjects were observed. The value of TG in homozygous C/C of the CHD is lower in heterozygote C/G of the CHD and in homozygous G/G of the CHD (C/CVSC/G,q=7.1224,P<0.01 ;C/CVSG/G,q=3.5441,P<0.05). The value of LDL-C in homozygous C/G of the CHD is lower in heterozygote C/G of the CHD and in homozygous G/G of the CHD (C/CVSC/G,q=3.6986,P<0.05;C/CVSG/G,q=2.9384,P<0.05). The value of TG in homozygous G/G of the controls is higher in heterozygote C/G of the CHD and in homozygous C/C of the controls (G/GVSC/C,q=3.4038,P<0.05; G/GVSC/G,q=4.3349,P<0.01).
5.Significant difference of genotypic frequencies of -3971A>G polymorphism in apM1 gene between the T2DM patient and control subjects in hypotype of A/C in -12601bp PPARagene were observed(x2=11.2, P<0.05)and significant difference of genotypic frequencies of -3971A>G polymorphism in apM1 gene between the T2DM patient and control subjects in hypotype of C/C in -12601bp PPARagene were observed(x2=10.3. P<0.05).Significant difference of genotypic frequencies of +4544C>G polymorphism in apM1 gene between the CHD patient、T2DM patient and control subjects in hypotype of A/C in -12601bp PPARagene were observed(x2=20.9, P<0.05; x2=12.5, P<0.05).
Significant difference of genotypic frequencies of -3971A>G polymorphism in apM1 gene between the CHD patient and control subjects in hypotype of G/G in -20337bp PPARagene were observed(x2=6.18, P<0.05).
Significant difference of genotypic frequencies of + 4544C>G polymorphism in apM1 gene between the CHD patient and control subjects in hypotype of A/A in -20337bp PPARagene were observed(x2=13.4, P<0.05)and significant difference of genotypic frequencies of +4544C>G polymorphism in apM1 gene between the CHD patient、the NIDDM patient and control subjects in hypotype of C/C in -20337bp PPARagene were observed(x2=16.6,P<0.05; x2=7.65,P<0.05).
Conclusion:Our investigation provided the evidence that the association is found between the apM1+4544C>G polymorphism and CHD , There is no significant correlation between the PPARa -12601A>C polymorphism、PPARa-20337A>G polymorphism、apM1-3971A>G polymorphism and CHD. There is no significant correlation between the PPARa -12601A>C polymorphism、PPARa-20337A>G polymorphism、apM1-3971A>G polymorphism apM1+4544C>G and T2DM . There is significant correlation between the PPARa -12601A>C polymorphism、PPARa-20337A>G polymorphism、apM1-3971A>G polymorphism apM1+4544C>G and blood fat in CHD group and T2DM group . The synergistic effect of PPARa gene and apM1gene has an effect on CHD and T2DM.
方法:以369例CHD患者、401例T2DM患者、339例正常对照为研究对象,采用PCR-RFLP技术对PPARa基因-12601A>C、PPARa基因-20337A>G、apM1基因-3971G>A、apM1基因+4544C>G多态位点的基因型和等位基因频率分布,应用SPSS 12.0软件对四种基因多态的不同基因型与血脂水平进行比较、PPARa基因两多态位点各亚型中apM1基因各亚型在CHD、T2DM及正常对照组中的分布进行分析。
结果:1.PPARa基因-12601A>C多态性: CHD组、T2DM组和对照组之间基因型分布及等位基因频率无显著性差别(P均>0.05)。CHD组中的A/A纯合子的TG值显著低于C/C纯合子(A/AVSC/C,q=3.9644,P<0.05), A/A纯合子的TC值显著低于A/C杂合子和C/C纯合子(A/AVSA/C,q=7.88,P<0.01;A/AVSC/C,q=4.2867,P<0.01)。T2DM组中的A/A纯合子的TG值显著低于A/C杂合子和C/C纯合子(A/AVSA/C,q=3.1570,P<0.05;A/AVSC/C,q=4.2867,P<0.01)。
2. PPARa基因-20337A>G多态性: CHD组、T2DM组与对照组之间基因型分布及等位基因频率无显著性差别(P均>0.05)。CHD组中A/A纯合子的TG值显著低于A/G杂合子和G/G纯合子(A/AVSA/G,q=4.5245,P<0.01;A/AVSG/G,q=5.2867,P<0.01)。T2DM组中的A/A纯合子的TG值低于A/G杂合子和G/G纯合子(A/AVSA/G,q=3.6986,P<0.05;A/AVSG/G,q=2.9384,P<0.05)及A/A纯合子的HDL-C值高于A/G杂合子和G/G纯合子(A/AVSA/G,q=3.157,P<0.05;A/AVSG/G, q=3.7857,P<0.05)。正常对照组中的A/G杂合子的TC值显著高于G/G纯合子(A/GVSG/G,q=3.5954,P<0.05)。
3.apM1基因-3971A>G多态性: CHD组、T2DM组与对照组之间基因型分布及等位基因频率无显著性差别(P均>0.05)。CHD组中A/A纯合子的TG值显著低于A/G杂合子和G/G纯合子(A/AVSA/G,q=3.9644,P<0.05 ;A/AVSG/G,q=4.2867,P<0.01), A/A纯合子的LDL-C值低于A/G杂合子和G/G纯合子(A/AVSA/G,q=7.88,P<0.01;A/AVSG/G, q=4.2867,P<0.01)。T2DM组中A/A纯合子的TG值低于A/G杂合子和G/G纯合子(A/AVSA/G,q=3.5242,P<0.05 ;A/AVSG/G,q=3.5813,P<0.05)。
4. apM1基因+4544C>G多态性: CHD组、T2DM组和对照组之间基因型分布无显著性差别(P均>0.05)。apM1基因+4544C>G多态的等位基因频率分布在T2DM患者和正常对照中没差别,因此可认为apM1基因+4544C>G多态性与T2DM无相关性。在CHD组中apM1基因+4544C稀有等位基因频率高于对照组并有显著性的差别,因此可认为apM1基因+4544C>G多态性与CHD存在相关性。CHD组中C/C纯合子的TG值显著低于C/G杂合子和G/G纯合子(C/CVSC/G,q=7.1224,P<0.01 ;C/CVSG/G,q=3.5441,P<0.05), C/C纯合子的LDL-C值显著低于C/G杂合子和G/G纯合子(C/CVSC/G,q=3.6986,P<0.05;C/CVSC/G,q=2.9384,P<0.05)。对照组中的G/G纯合子的TG值显著高于C/C纯合子和C/G杂合子(G/GVSC/C,q=3.4038,P<0.05; G/GVSC/G,q=4.3349,P<0.01)。
5. PPARa基因的-12601A>C多态性AC亚型中apM1基因-3971A>G基因型在T2DM组与正常对照组分布有显著性的差别(x2=11.2, P<0.05)。PPARa基因的-12601A>C多态性CC亚型中apM1基因-3971A>G的各亚型在T2DM组与正常对照组中分布不同(x2=11.2, P<0.05)。PPARa基因的-12601A>C多态性AC亚型中apM1基因+4544C>G的各亚型在CHD组和T2DM组与正常对照组分布不同(x2=20.9, P<0.05; x2=12.5, P<0.05)。
PPARa基因的-20337A>G多态性GG亚型中apM1基因-3971A>G的各亚型在CHD组与正常对照组中的分布不同(x2=6.18, P<0.05)。PPARa基因的-20337A>G多态性AA亚型中apM1基因+4544C>G的各亚型在CHD组与正常对照组中的分布不同(x2=13.4, P<0.05)。PPARa-20337AG基因亚型中apM1+4544C>G基因型在CHD组、T2DM组与正常对照组分布不同(x2=16.6,P<0.05; x2=7.65,P<0.05)。
结论:上述结果表明,PPARa基因-12601A>C多态性、PPARa基因的-20337A>G多态性、apM1基因-3971A>G多态性及apM1基因+4544C>G多态性与T2DM不存在相关性。PPARa-12601A>C多态性、PPARa基因的-20337A>G多态性、apM1基因-3971A>G多态性与CHD不存在相关性,但apM1基因+4544C>G多态性与CHD存在相关性。PPARa基因-12601A>C多态性与CHD和T2DM中的血脂有关,PPARa基因的-20337A>G多态性与T2DM中的血脂有关,apM1基因-3971A>G多态性与CHD和T2DM的血脂有关,apM1基因+4544C>G多态性与CHD的血脂有关。PPARa基因多态性与apM1基因多态性协同作用对CHD和T2DM有影响。
Objective: Many epidemiological studies and reviews have demonstrated that dyslipidemia was associated with heterogeneity of the onset and severity of coronary heart disease (CHD), in addition, it is also a clinical feature of type 2 diabetes mellitus (T2DM), and then it has been proposed to be a risk factor for T2DM. The purpose of this study was to evaluate the influence of variants in the lipid metabolism related genes peroxisome proliferators-activated receptor-a(PPARa)、apM1 on the risk of developing CHD and T2DM and the effect between the two genes interaction CHD and T2DM. These variants were -12601A>C and -20337A>G polymorphisms in the PPARa gene,-3971 A>G and +4544 C>G polymorphisms in apM1 gene.
Methods: We examined these four single nucleotide polymorphisms (SNPs)( -12601A>C and -20337A>G polymorphisms in the PPARa gene, -3971A>G and C4544G polymorphisms in the apM1 gene) in 369 patients with CHD,401 patients with T2DM and in 339 controls by PCR-RFLP. Then,we analysed the association of these SNPs with lipid metabolism in patients with CHD、T2DM and controls. Case-control comparisons were performed separately for CHD、T2DM and controls by using SPSS statistical software package.
Results: 1.No significant difference of allelic or genotypic frequencies either of -12601A>C polymorphism in PPARa gene between the CHD、T2DM patient and control subjects were observed.The value of TG in homozygous A/A of the CHD is lower in homozygous C/C of the CHD(A/AVSA/C,q=3.9644,P<0.05). The value of TC in homozygous A/A of the CHD is lower in heterozygote A/C of the CHD and in homozygous C/C of the CHD(A/AVSA/C,q=7.88,P<0.01;A/AVSC/C,q=4.2867,P<0.01) . The value of TG in homozygous A/A of the T2DM is lower in heterozygote A/C of the CHD and in homozygous C/C of the (A/AVSA/C,q=3.1570,P<0.05;A/AVSC/C,q=4.2867,P<0.01)
2. No significant difference of allelic or genotypic frequencies either of -20337A>G polymorphism in PPARa gene between the CHD, T2DM patient and control subjects were observed.The value of TG in homozygous A/A of the CHD is lower in heterozygote A/G of the CHD and in homozygous G/G of the CHD (A/AVSA/G,q=4.5245,P<0.01;A/AVSG/G,q=5.2867,P<0.01). The value of TG in homozygous A/A of the T2DM is lower in heterozygote A/G of the T2DM and in homozygous G/G of the CHD (A/AVSA/G,q=3.6986,P<0.05;A/AVSG/G,q=2.9384,P<0.05). The value of HDL-C in homozygous A/A of theT2DM is higher in heterozygote A/C of the T2DM and in homozygous G/G of the T2DM ((A/AVSA/G,q=3.157,P<0.05;A/AVSG/G,q=3.7857,P<0.05)) . The value of TG in heterozygote A/G of the controls is higher in homozygous G/G of the controls (A/GVSG/G,q=3.5954,P<0.05).
3.No significant difference of allelic or genotypic frequencies either of -3971A>G polymorphism in apM1 gene between the CHD, T2DM patient and control subjects were observed.The value of TG in homozygous A/A of the CHD is lower in heterozygote A/G of the CHD and in homozygous G/G of the CHD (A/AVSA/G,q=3.9644,P<0.05 ;A/AVSG/G,q=4.2867,P<0.01). The value of LDL-C in homozygous A/A of the CHD is lower in heterozygote A/G of the CHD and in homozygous G/G of the CHD ((A/AVSA/G,q=7.88,P<0.01;A/AVSG/G,q=4.2867,P<0.01)。The value of TG in homozygous A/A of the T2DM is higher in heterozygote A/C of the CHD and in homozygous G/G of the T2DM (A/AVSA/G,q=3.5242,P<0.05 ;A/AVSG/G,q=3.5813,P<0.05).
4. No significant difference of allelic or genotypic frequencies either of +4544C>G polymorphism in apM1 gene between the CHD patient and control subjects were observed. No significant difference of genotypic frequencies either of +4544C>G polymorphism in apM1 gene between the T2DM patient and control subjects were observed.There is significant difference of allelic frequencies either of +4544C>G polymorphism in apM1 gene between the T2DM patient and control subjects were observed. The value of TG in homozygous C/C of the CHD is lower in heterozygote C/G of the CHD and in homozygous G/G of the CHD (C/CVSC/G,q=7.1224,P<0.01 ;C/CVSG/G,q=3.5441,P<0.05). The value of LDL-C in homozygous C/G of the CHD is lower in heterozygote C/G of the CHD and in homozygous G/G of the CHD (C/CVSC/G,q=3.6986,P<0.05;C/CVSG/G,q=2.9384,P<0.05). The value of TG in homozygous G/G of the controls is higher in heterozygote C/G of the CHD and in homozygous C/C of the controls (G/GVSC/C,q=3.4038,P<0.05; G/GVSC/G,q=4.3349,P<0.01).
5.Significant difference of genotypic frequencies of -3971A>G polymorphism in apM1 gene between the T2DM patient and control subjects in hypotype of A/C in -12601bp PPARagene were observed(x2=11.2, P<0.05)and significant difference of genotypic frequencies of -3971A>G polymorphism in apM1 gene between the T2DM patient and control subjects in hypotype of C/C in -12601bp PPARagene were observed(x2=10.3. P<0.05).Significant difference of genotypic frequencies of +4544C>G polymorphism in apM1 gene between the CHD patient、T2DM patient and control subjects in hypotype of A/C in -12601bp PPARagene were observed(x2=20.9, P<0.05; x2=12.5, P<0.05).
Significant difference of genotypic frequencies of -3971A>G polymorphism in apM1 gene between the CHD patient and control subjects in hypotype of G/G in -20337bp PPARagene were observed(x2=6.18, P<0.05).
Significant difference of genotypic frequencies of + 4544C>G polymorphism in apM1 gene between the CHD patient and control subjects in hypotype of A/A in -20337bp PPARagene were observed(x2=13.4, P<0.05)and significant difference of genotypic frequencies of +4544C>G polymorphism in apM1 gene between the CHD patient、the NIDDM patient and control subjects in hypotype of C/C in -20337bp PPARagene were observed(x2=16.6,P<0.05; x2=7.65,P<0.05).
Conclusion:Our investigation provided the evidence that the association is found between the apM1+4544C>G polymorphism and CHD , There is no significant correlation between the PPARa -12601A>C polymorphism、PPARa-20337A>G polymorphism、apM1-3971A>G polymorphism and CHD. There is no significant correlation between the PPARa -12601A>C polymorphism、PPARa-20337A>G polymorphism、apM1-3971A>G polymorphism apM1+4544C>G and T2DM . There is significant correlation between the PPARa -12601A>C polymorphism、PPARa-20337A>G polymorphism、apM1-3971A>G polymorphism apM1+4544C>G and blood fat in CHD group and T2DM group . The synergistic effect of PPARa gene and apM1gene has an effect on CHD and T2DM.
引文
1. Berenson GS, Srinivasan SR, Wattigney WA, et al. Obesity and cardiovascular risk in children. Ann N Y Acad Sci, 1993 Oct 29;699:93-103.
2. Satoh H, Nishino T, Tomita K, et al. Fasting triglyceride is a significant risk factor for coronary artery disease in middle-aged Japanese men. Circ J, 2006 Mar;70(3):227-231.
3. Xydakis AM, Ballantyne CM. Role of non-high-density lipoprotein cholesterol in prevention of cardiovascular disease: updated evidence from clinical trials. Curr Opin Cardiol, 2003 Nov;18(6):503-509.
4. Iso H, Naito Y, Sato S, et al. Serum triglycerides and risk of coronary heart disease among Japanese men and women. Am J Epidemiol, 2001 Mar 1;153(5):490-499.
5. Manninen V, Tenkanen L, Koskinen P, et al. Joint effects of serum triglyceride and LDL cholesterol and HDL cholesterol concentrations on coronary heart disease risk in the Helsinki Heart Study. Implications for treatment. Circulation, 1992 Jan;85(1):37-45.
6. Hokanson JE, Austin MA. Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J Cardiovasc Risk, 1996; 3: 213–219.
7. Miller GJ, Miller NE. Plasma-high-density-lipoprotein concentration and development of ischaemic heart-disease. Lancet, 1975 Jan 4;1(7897):16-19.
8. Kannel WB, Castelli WP, Gordon T. Cholesterol in the prediction of atherosclerotic disease. New perspectives based on the Framingham study. Ann Intern Med, 1979;90:85–91.
9. Gordon DJ, Probstfield JL, Garrison RJ, et al. High-densitylipoprotein cholesterol and cardiovascular disease: four prospective American studies. Circulation, 1989;79:8–15.
10.华琦,汤哲. 北京市老年人群体重、血脂、血压及血糖水平的调查与分析. 中华内科杂志,1997;36(1):18-20.
11.Ali I, Khan IU, Baloch MK, et al. Comparative lipid profile studies in cardiac and diabetic conditions. Pak J Pharm Sci, 2004 ;Jan;17(1):25-30.
12.van Tilburg J, van Haeften TW, Pearson P, et al. Defining the genetic contribution of type 2 diabetes mellitus. J Med Genet, 2001 Sep;38(9):569-578.
13.Talmud PJ,Stephens JW.Lipoprotrin lipase gene xariants and the effect of environmental factors on cardiovascular disease risk.Diabetes Obes Metab.2004,6(1):1-7.
14.SteinbergD,Gotto AM.Precenting coronary artery disease by lowering cholesterol levels:fifty years from bench to bedside.JAMA.1999,282:2043-2050.
15.Hokason JE, Austin MA.Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level:a meta-analysis of population-based prodpective studies.J Cardiovasc Risk1996,3:213-219.
16.Lacquemnat C ,Lepretre F ,Pinend Torre I ,et al. Mutation screening of the PPARα gene in type 2 diabetes association with coronary heart disease[J]. Diabetes Metab, 2000,26(5):393-401.
17. Heinlein CA,Ting HJ,Yeh S,et al. Identification of ARA70 as a ligand-enhanced coactivator for the peroxisome proliferator-activated receptor gamma. [J].J Biol Chem, 1999,274(23):16147-16152.
18. Schoonjans K,Staels B,Auwerx J.The peroxisome proliferator activated receptors (PPARS) and their effects on lipid metabolism andadipocyte differentiation[J].Biochim Biophys Acta,1996,1302 (2):93-109.
19.Schoonjans K,Staels B,Auwerx J.Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression[J].J Lipid Res ,1996,37(5):907-925.
20.Cnop M, Havel PJ, Utzschneider KM, et al. Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex[J]. Diabetologia , 2003, 46 (4) : 459-469.
21.Hotta K, Funahashi T, Arita Y, et al. Plasma concentrations of anovel, adipose-specific protein, adiponectin, in type 2 diabetic Patients [ J ]. Arterioscler Thromb Vasc Biol, 2000, 20 ( 6) : 1595-1599.
22.Hotta K,Funahashi T,Arita Y,et al. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol, 2000,20:1595-1599.
23.Yamauchi T, Kamon J, Minokoshi Y, et al. Adiponectin stimulates glucose utilization and fatty2acid oxidation by activating AMP-activated p rotein kinase [ J ]. Nat Med, 2002, 8 ( 11 ) :1288-1295.
24.Yamauchi T, Kamon J, Waki H, et al. Globular adiponectin protected ob /ob mice from diabetes and ApoE2deficient mice from atherosclerosis[ J ]. J Biol Chem, 2003, 278 (4): 2461-2468.
25.Weyer C,Funahasi T,Tannka S ,et al.Hypoadiponectinmia in obesity and type 2diabetes:close association with insulin resistance and hyperinsulinemia. [J] Clin Endocrinal Metab,2001,86:1930-1935.
26. Issemann I,Green S.Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators [J].Nature,1990,347 (6294): 645-650.
27. Vohl MC, Lepage P, Gaudet D, et al. Molecular scanning of the humanPPARa gene: association of the L162v mutation with hyperapobetalipoproteinemia [J]. J Lipid Res, 2000 ,41(6):945-952.
28. Flavell DM, Pineda TI, Jamshidi Y, et al. Variation in the PPARα gene is associated with altered function in vitro and plasma lipid concentrations in type Ⅱ diabetic subjects[J]. Diabetologia, 2000, 43(5): 673-680.
29. Evans D , Aberle J , Wendt D , et al. A polymorphism, L162V,in the peroxisome proliferator-activated receptor alpha (PPARalpha) gene is associated with lower body mass index in patients with non-insulin-dependent diabetes mellitus[J].J Mol Med ,2001,79(4):198-204.
30. Tai ES, Demissie S, Cupples LA, et al. Association between the PPARA L162V polymorphism and plasma lipid levels: the Framingham Offspring Study[J]. Arterioscler Thromb Vasc Biol ,2002 ,22(5):805-810.
31. Eurlings PM, van der Kallen CJ, Geurts JM, et al. Identification of the PPARA locus on chromosome 22q13.3 as a modifier gene in familial combined hyperlipidemia[J]. Mol Genet Metab,2002,77(4):274-281.
32.Scherer PE, Willians S,Fogliano M,et al.A novel scrum protein similar to Clq, produced exclusively in adipocytes. [J] Biol Chem,1995,270:26746-26749.
33. Gearing KL., Crickmore A, and Gustafsson JA. Structure of the Mouse Peroxisome Proliferator Activated Receptor alpha Gene[J].Biochem Biophys Res Commun. 1994,199(1):255-263.
34.Takahashi M, Arita Y, Yamagata K,et al,Genonic structure and mutations in adipose-specific gene,adiponetin Int Jobes,2000,24:861-868.
35.Knodo H,Shimomura I,matsukawa Y,et al.Association of adiponectin mutation with type 2 diabetes,Diabetes,2002,51:2325-2328.
36.Zietor B,Barth N,Scholmerich J,et al.Gly15Gly polymorphism within thehuman adipocyte-specific apm-1 gene but not Tyr111His polymorphism is associated with higher levels of cholesterol and LDL-cholesterol in Cancasian patient with type 2 diabetes.Exp Clin Endocrinol Diabetes,2001,109:320-325.
37.StumorII M,Tschritter O,Fritsche A,et al.Association of the T-G polymorphism in adiponectin(exon 2),with obesity and insulin sensitivity.Diabetes,2002,51:37-41.
38.Lihn AS,Ostergard T,Nyholm B,et al.Adiponection expression in adipose tissue is reduced in first-degree relative of type 2 diabetic patients.Am J Physiol endocrinol Metab,2003,284:E443-E448.
[1]Issemann I,Green S.Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators [J].Nature,1990,347 (6294): 645-650.
[2] Heinlein CA,Ting HJ,Yeh S,et al. Identification of ARA70 as a ligand-enhanced coactivator for the peroxisome proliferator-activated receptor gamma. [J].J Biol Chem, 1999,274(23):16147-16152.
[3] Schoonjans K,Staels B,Auwerx J.The peroxisome proliferator activated receptors (PPARS) and their effects on lipid metabolism and adipocyte differentiation[J].Biochim Biophys Acta,1996,1302(2):93-109.
[4] Schoonjans K,Staels B,Auwerx J.Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression[J].J Lipid Res ,1996,37(5):907-925.
[5] Lacquemnat C ,Lepretre F ,Pinend Torre I ,et al. Mutation screening of the PPARα gene in type 2 diabetes association with coronary heart disease[J]. Diabetes Metab, 2000,26(5):393-401.
[6] Gearing KL., Crickmore A, and Gustafsson JA. Structure of the Mouse Peroxisome Proliferator Activated Receptor alpha Gene[J].Biochem Biophys Res Commun. 1994,199(1):255-263.
[7] Balcerzyk A, Zak I, Krauze J. Synergistic effect between polymorphisms of PPARA and ABCA1 genes on the premature coronary artery disease[J]. Acta Cardiol, 2007, 62(3):233-238.
[8] Andrulionyte L,Kuulasmaa T,Chiasson JL,et al. Single nucleotide polymorphisms of the peroxisome proliferator-activated receptor-alpha gene (PPARA) influence the conversion from impaired glucose tolerance to type 2 diabetes: the STOP-NIDDM trial. [J]. Diabetes, 2007,56(4):1181-1186.
[9] Doney AS,Fischer B,Lee SP,et al.Association of common variationin the PPARA gene with incident myocardial infarction in individuals with type 2 diabetes : A Go-DARTS study[J/OL].http//www.nuclear-receptor.com/content/3/1/4.html ,2005-11-25/2007-08-08.
[10] Mossner R, Kaiser R, Matern P, et al. Variations in the genes encoding the peroxisome proliferator-activated receptors α and γ in psoriasis[J]. Arch Dermatol Res, 2004,296(1):1-5.
[11] Vohl MC, Lepage P, Gaudet D, et al. Molecular scanning of the human PPARa gene: association of the L162v mutation with hyperapobetalipoproteinemia [J]. J Lipid Res, 2000 , 41(6):945-952.
[12] Flavell DM, Jamshidi Y, Hawe E, et al. Peroxisome Proliferator-Activated Receptor alpha Gene Variants Influence Progression of Coronary Atherosclerosisand Risk of Coronary Artery Disease[J].Circulation,2002,105(12):1440-1445.
[13] Flavell DM, Pineda TI, Jamshidi Y, et al. Variation in the PPARα gene is associated with altered function in vitro and plasma lipid concentrations in type Ⅱ diabetic subjects[J]. Diabetologia, 2000, 43(5): 673-680.
[14] Evans D , Aberle J , Wendt D , et al. A polymorphism, L162V,in the peroxisome proliferator-activated receptor alpha (PPARalpha) gene is associated with lower body mass index in patients with non-insulin-dependent diabetes mellitus[J].J Mol Med ,2001,79(4):198-204.
[15] Tai ES, Demissie S, Cupples LA, et al. Association between the PPARA L162V polymorphism and plasma lipid levels: the Framingham Offspring Study[J]. Arterioscler Thromb Vasc Biol ,2002 ,22(5):805-810.
[16] Eurlings PM, van der Kallen CJ, Geurts JM, et al. Identification of the PPARA locus on chromosome 22q13.3 as a modifier gene in familial combined hyperlipidemia[J]. Mol Genet Metab,2002,77(4):274-281.
[17] 张颖,雷红,,邓幼平. 2 型糖尿病患者PPARα基因多态性的研究[J].武汉大学学报(医学版),2004 ,25(4): 459-461.
[18] 张萍,苏本利,于军,等.过氧化物酶体增殖物激活受体α基因L162V变异与血脂异常的关系[J].中华内分泌代谢杂志,2005,21(2): 148-149.
[19] 李全民,张素华,任伟,等.过氧化物酶体增殖物激活受体α基因突变与2型糖尿病家系血脂的关系[J].中华糖尿病杂志,2004,12(1):41-42.
2. Satoh H, Nishino T, Tomita K, et al. Fasting triglyceride is a significant risk factor for coronary artery disease in middle-aged Japanese men. Circ J, 2006 Mar;70(3):227-231.
3. Xydakis AM, Ballantyne CM. Role of non-high-density lipoprotein cholesterol in prevention of cardiovascular disease: updated evidence from clinical trials. Curr Opin Cardiol, 2003 Nov;18(6):503-509.
4. Iso H, Naito Y, Sato S, et al. Serum triglycerides and risk of coronary heart disease among Japanese men and women. Am J Epidemiol, 2001 Mar 1;153(5):490-499.
5. Manninen V, Tenkanen L, Koskinen P, et al. Joint effects of serum triglyceride and LDL cholesterol and HDL cholesterol concentrations on coronary heart disease risk in the Helsinki Heart Study. Implications for treatment. Circulation, 1992 Jan;85(1):37-45.
6. Hokanson JE, Austin MA. Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J Cardiovasc Risk, 1996; 3: 213–219.
7. Miller GJ, Miller NE. Plasma-high-density-lipoprotein concentration and development of ischaemic heart-disease. Lancet, 1975 Jan 4;1(7897):16-19.
8. Kannel WB, Castelli WP, Gordon T. Cholesterol in the prediction of atherosclerotic disease. New perspectives based on the Framingham study. Ann Intern Med, 1979;90:85–91.
9. Gordon DJ, Probstfield JL, Garrison RJ, et al. High-densitylipoprotein cholesterol and cardiovascular disease: four prospective American studies. Circulation, 1989;79:8–15.
10.华琦,汤哲. 北京市老年人群体重、血脂、血压及血糖水平的调查与分析. 中华内科杂志,1997;36(1):18-20.
11.Ali I, Khan IU, Baloch MK, et al. Comparative lipid profile studies in cardiac and diabetic conditions. Pak J Pharm Sci, 2004 ;Jan;17(1):25-30.
12.van Tilburg J, van Haeften TW, Pearson P, et al. Defining the genetic contribution of type 2 diabetes mellitus. J Med Genet, 2001 Sep;38(9):569-578.
13.Talmud PJ,Stephens JW.Lipoprotrin lipase gene xariants and the effect of environmental factors on cardiovascular disease risk.Diabetes Obes Metab.2004,6(1):1-7.
14.SteinbergD,Gotto AM.Precenting coronary artery disease by lowering cholesterol levels:fifty years from bench to bedside.JAMA.1999,282:2043-2050.
15.Hokason JE, Austin MA.Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level:a meta-analysis of population-based prodpective studies.J Cardiovasc Risk1996,3:213-219.
16.Lacquemnat C ,Lepretre F ,Pinend Torre I ,et al. Mutation screening of the PPARα gene in type 2 diabetes association with coronary heart disease[J]. Diabetes Metab, 2000,26(5):393-401.
17. Heinlein CA,Ting HJ,Yeh S,et al. Identification of ARA70 as a ligand-enhanced coactivator for the peroxisome proliferator-activated receptor gamma. [J].J Biol Chem, 1999,274(23):16147-16152.
18. Schoonjans K,Staels B,Auwerx J.The peroxisome proliferator activated receptors (PPARS) and their effects on lipid metabolism andadipocyte differentiation[J].Biochim Biophys Acta,1996,1302 (2):93-109.
19.Schoonjans K,Staels B,Auwerx J.Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression[J].J Lipid Res ,1996,37(5):907-925.
20.Cnop M, Havel PJ, Utzschneider KM, et al. Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex[J]. Diabetologia , 2003, 46 (4) : 459-469.
21.Hotta K, Funahashi T, Arita Y, et al. Plasma concentrations of anovel, adipose-specific protein, adiponectin, in type 2 diabetic Patients [ J ]. Arterioscler Thromb Vasc Biol, 2000, 20 ( 6) : 1595-1599.
22.Hotta K,Funahashi T,Arita Y,et al. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol, 2000,20:1595-1599.
23.Yamauchi T, Kamon J, Minokoshi Y, et al. Adiponectin stimulates glucose utilization and fatty2acid oxidation by activating AMP-activated p rotein kinase [ J ]. Nat Med, 2002, 8 ( 11 ) :1288-1295.
24.Yamauchi T, Kamon J, Waki H, et al. Globular adiponectin protected ob /ob mice from diabetes and ApoE2deficient mice from atherosclerosis[ J ]. J Biol Chem, 2003, 278 (4): 2461-2468.
25.Weyer C,Funahasi T,Tannka S ,et al.Hypoadiponectinmia in obesity and type 2diabetes:close association with insulin resistance and hyperinsulinemia. [J] Clin Endocrinal Metab,2001,86:1930-1935.
26. Issemann I,Green S.Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators [J].Nature,1990,347 (6294): 645-650.
27. Vohl MC, Lepage P, Gaudet D, et al. Molecular scanning of the humanPPARa gene: association of the L162v mutation with hyperapobetalipoproteinemia [J]. J Lipid Res, 2000 ,41(6):945-952.
28. Flavell DM, Pineda TI, Jamshidi Y, et al. Variation in the PPARα gene is associated with altered function in vitro and plasma lipid concentrations in type Ⅱ diabetic subjects[J]. Diabetologia, 2000, 43(5): 673-680.
29. Evans D , Aberle J , Wendt D , et al. A polymorphism, L162V,in the peroxisome proliferator-activated receptor alpha (PPARalpha) gene is associated with lower body mass index in patients with non-insulin-dependent diabetes mellitus[J].J Mol Med ,2001,79(4):198-204.
30. Tai ES, Demissie S, Cupples LA, et al. Association between the PPARA L162V polymorphism and plasma lipid levels: the Framingham Offspring Study[J]. Arterioscler Thromb Vasc Biol ,2002 ,22(5):805-810.
31. Eurlings PM, van der Kallen CJ, Geurts JM, et al. Identification of the PPARA locus on chromosome 22q13.3 as a modifier gene in familial combined hyperlipidemia[J]. Mol Genet Metab,2002,77(4):274-281.
32.Scherer PE, Willians S,Fogliano M,et al.A novel scrum protein similar to Clq, produced exclusively in adipocytes. [J] Biol Chem,1995,270:26746-26749.
33. Gearing KL., Crickmore A, and Gustafsson JA. Structure of the Mouse Peroxisome Proliferator Activated Receptor alpha Gene[J].Biochem Biophys Res Commun. 1994,199(1):255-263.
34.Takahashi M, Arita Y, Yamagata K,et al,Genonic structure and mutations in adipose-specific gene,adiponetin Int Jobes,2000,24:861-868.
35.Knodo H,Shimomura I,matsukawa Y,et al.Association of adiponectin mutation with type 2 diabetes,Diabetes,2002,51:2325-2328.
36.Zietor B,Barth N,Scholmerich J,et al.Gly15Gly polymorphism within thehuman adipocyte-specific apm-1 gene but not Tyr111His polymorphism is associated with higher levels of cholesterol and LDL-cholesterol in Cancasian patient with type 2 diabetes.Exp Clin Endocrinol Diabetes,2001,109:320-325.
37.StumorII M,Tschritter O,Fritsche A,et al.Association of the T-G polymorphism in adiponectin(exon 2),with obesity and insulin sensitivity.Diabetes,2002,51:37-41.
38.Lihn AS,Ostergard T,Nyholm B,et al.Adiponection expression in adipose tissue is reduced in first-degree relative of type 2 diabetic patients.Am J Physiol endocrinol Metab,2003,284:E443-E448.
[1]Issemann I,Green S.Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators [J].Nature,1990,347 (6294): 645-650.
[2] Heinlein CA,Ting HJ,Yeh S,et al. Identification of ARA70 as a ligand-enhanced coactivator for the peroxisome proliferator-activated receptor gamma. [J].J Biol Chem, 1999,274(23):16147-16152.
[3] Schoonjans K,Staels B,Auwerx J.The peroxisome proliferator activated receptors (PPARS) and their effects on lipid metabolism and adipocyte differentiation[J].Biochim Biophys Acta,1996,1302(2):93-109.
[4] Schoonjans K,Staels B,Auwerx J.Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression[J].J Lipid Res ,1996,37(5):907-925.
[5] Lacquemnat C ,Lepretre F ,Pinend Torre I ,et al. Mutation screening of the PPARα gene in type 2 diabetes association with coronary heart disease[J]. Diabetes Metab, 2000,26(5):393-401.
[6] Gearing KL., Crickmore A, and Gustafsson JA. Structure of the Mouse Peroxisome Proliferator Activated Receptor alpha Gene[J].Biochem Biophys Res Commun. 1994,199(1):255-263.
[7] Balcerzyk A, Zak I, Krauze J. Synergistic effect between polymorphisms of PPARA and ABCA1 genes on the premature coronary artery disease[J]. Acta Cardiol, 2007, 62(3):233-238.
[8] Andrulionyte L,Kuulasmaa T,Chiasson JL,et al. Single nucleotide polymorphisms of the peroxisome proliferator-activated receptor-alpha gene (PPARA) influence the conversion from impaired glucose tolerance to type 2 diabetes: the STOP-NIDDM trial. [J]. Diabetes, 2007,56(4):1181-1186.
[9] Doney AS,Fischer B,Lee SP,et al.Association of common variationin the PPARA gene with incident myocardial infarction in individuals with type 2 diabetes : A Go-DARTS study[J/OL].http//www.nuclear-receptor.com/content/3/1/4.html ,2005-11-25/2007-08-08.
[10] Mossner R, Kaiser R, Matern P, et al. Variations in the genes encoding the peroxisome proliferator-activated receptors α and γ in psoriasis[J]. Arch Dermatol Res, 2004,296(1):1-5.
[11] Vohl MC, Lepage P, Gaudet D, et al. Molecular scanning of the human PPARa gene: association of the L162v mutation with hyperapobetalipoproteinemia [J]. J Lipid Res, 2000 , 41(6):945-952.
[12] Flavell DM, Jamshidi Y, Hawe E, et al. Peroxisome Proliferator-Activated Receptor alpha Gene Variants Influence Progression of Coronary Atherosclerosisand Risk of Coronary Artery Disease[J].Circulation,2002,105(12):1440-1445.
[13] Flavell DM, Pineda TI, Jamshidi Y, et al. Variation in the PPARα gene is associated with altered function in vitro and plasma lipid concentrations in type Ⅱ diabetic subjects[J]. Diabetologia, 2000, 43(5): 673-680.
[14] Evans D , Aberle J , Wendt D , et al. A polymorphism, L162V,in the peroxisome proliferator-activated receptor alpha (PPARalpha) gene is associated with lower body mass index in patients with non-insulin-dependent diabetes mellitus[J].J Mol Med ,2001,79(4):198-204.
[15] Tai ES, Demissie S, Cupples LA, et al. Association between the PPARA L162V polymorphism and plasma lipid levels: the Framingham Offspring Study[J]. Arterioscler Thromb Vasc Biol ,2002 ,22(5):805-810.
[16] Eurlings PM, van der Kallen CJ, Geurts JM, et al. Identification of the PPARA locus on chromosome 22q13.3 as a modifier gene in familial combined hyperlipidemia[J]. Mol Genet Metab,2002,77(4):274-281.
[17] 张颖,雷红,,邓幼平. 2 型糖尿病患者PPARα基因多态性的研究[J].武汉大学学报(医学版),2004 ,25(4): 459-461.
[18] 张萍,苏本利,于军,等.过氧化物酶体增殖物激活受体α基因L162V变异与血脂异常的关系[J].中华内分泌代谢杂志,2005,21(2): 148-149.
[19] 李全民,张素华,任伟,等.过氧化物酶体增殖物激活受体α基因突变与2型糖尿病家系血脂的关系[J].中华糖尿病杂志,2004,12(1):41-42.