MIF与PPARγ基因多态性及其交互作用与脑卒中的关联研究
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摘要
目的:
(1)探讨中国湖南汉族人群中MIF基因-173G/C多态性和PPARγ基因C1431T多态性及其交互作用与脑卒中的关系。
(2)探讨中国湖南汉族人群中MIF基因-173G/C多态性和PPARγ基因C1431T多态性及其交互作用与血脂、血压、血糖的关系。
方法:采用PCR-RFLP技术检测和DNA测序技术验证298例脑梗死患者、162例脑出血患者和203例对照者MIF基因-173G/C和PPARγ基因C1431T 2个位点多态性分布,同时检测研究对象的血脂、血压、血糖、BMI及IMT水平,以上所得数据采用SPSS13.0进行数据分析。
结果:
(1)中国湖南地区汉族人群存在MIF-173G/C、PPARγC1431T多态性,正常对照组中等位基因频率分别是G/C 0.793/0.207,C/T0.798/0.202。脑梗死组、脑出血组MIF-173G/C基因型和等位基因分布频率与对照组一致(P＞0.05),而PPARγT/X基因型频率和T等位基因频率均显著高于对照组(P＜0.05),这种差异在合并糖尿病和高血压病患者中尤为明显。
(2)脑梗死组MIF—173 C/X基因型BMI水平显著高于-173GG纯合子(P＜0.05)。脑梗死组PPARγ1431T/X基因型与CC纯合子相比,FBS及LDL-c水平显著升高,HDL-c水平显著降低(P＜0.05);脑出血组T等位基因携带者TG水平显著高于CC纯合子(P＜0.05)。
(3)“PPARγ1431T/X”亚组中,“MIF—173C/X”基因型脑卒中的发生率显著高于“MIF—173GG”基因型(P＜0.05);脑梗死组“PPARγ1431 T/X”与“MIF—173 C/X”联合变异患高血压的发病风险较其它各联合基因型显著升高(P＜0.05)。脑出血组仅在“PPARγ1431 CC”亚型中,“MIF—173C/X”基因型较“MIF—173GG”基因型患高血压的风险显著增高(P＜0.05)。无论“PPARγ1431T/X”变异存在与否,“MIF—173C/X”基因型较“MIF—173GG”基因型患糖尿病的风险均显著增高(P＜0.05)。
(4)脑梗死“PPARγ1431CC”基因型中,“MIF—173C/X”基因型LDL-c水平显著低于“MIF-173 GG”纯合子(P＜0.05);在“1431T/X”基因型中,“MIF—173C/X”基因型LDL-c、舒张压、BMI水平均显著高于“MIF-173 GG”纯合子(P＜0.05).脑出血“PPARγ1431 T/X”基因型中,“MIF—173C/X”基因型BMI水平显著高于“MIF—173GG”纯合子(P＜0.05)。
结论
(1)MIF-173G/C多态性可能与中国湖南汉族人脑卒中发生无关,而PPARγC1431T多态性可能与之相关。
(2)MIF-173 C等位基因可能与脑梗死患者较高的BMI水平有关,PPARγC1431T多态性可能参与了血脂、血糖代谢。
(3)PPARγC1431T和MIF-173G/C多态性对血脂、血压、BMI水平可能存在交互作用,继而影响脑卒中的发生。
Objectives Epidemiologic studies have shown that serum level of both MIF and PPARγare implicated in several physiologic pathways such as hypertension,lipid metabolism,severity of insulin resistance, inflammatory reaction,and atherosclerosis,all of which are closely related to the pathogenesis of stroke.MIF and PPARγgene exhibit genetically determined structural polymorphisms.Until now,several polymerphisms, i.e.-173G/C,+254(T/C)and +656(C/G)for MIF,Pro12Ala and C1431T for PPARγ,respectively,have been identified.The aim of the present study was to investigate possible effects of MIF-173G/C and PPARγC1431T polymorphisms as well as the interaction between the two tested polymorphisms on the presence of stroke,hypertension,and serum lipid levels in Chinese Han population of Hunan area.
Methods A total of 203 healthy individuals,298 patients with with cerebral infarction(CI)and 162 patients with primary cerebral hemorrhage(CH)of Chinese origin were were recruited in this study.The genotypes for the two tested SNPs were detected by polymerase chain reaction-restrictive fragment length polymorphism(PCR—RFLP)and DNA sequence.Serum lipid concentrations were determined by enzymatic analytical chemistry.
Results
(1)-173G/C of MIF and C1431T of PPARγpolymorphisms exist in Chinese people of Hunan area,with the allele frequencies 0.793/0.207for—173G/C and 0.798/0.202 for 1431 C/T,respectively.No significant differences were observed in genotypes and allele frequencies between stroke patients and controls for MIF-173G/C polymorphism(P＞0.05).As to PPARγC1431T polymorphism,significant higher frequencies of T allele and T/X genotype were confirmed in stroke patients with respect to the control subjects(P＜0.05),especially in patients with hypertention and diabetes mellitus.
(2)The MIF-173C allele carriers in CI patients have significant higher level of BMI than-173GG homozygosis(P＜0.05).Compared to the PPARγ1431CC homozygosis,T allele carriers in CI patients have significant higher levels of FBS and LDL-c while low level of HDL-c; T allele carriers in CH subjects only have significantly higher level of TG(P＜0.05).
(3)The combined effects of these two genes on stroke risk were examined by subgroup analyses.The result indicated that there exhibited no significant difference between MIF-173 C and non-173C carriers in the incidence of stroke within the PPARγ1431CC genotype subgroup, but the difference appeared within the 1431T/X genotype subgroup, that is to say MIF-173 C allele carriers had a higher risk of stroke than the non-173C carriers(P＜0.05).The combination mutations of PPARγ1431 C-＞T and MIF -173G-＞C have the highest risk of hypertention in CI group(P＜0.05).The MIF -173C carriers in CH patients had a higher incidence of hypertention than the non-173Ccarriers within the PPARγCC genotype subgroup(P＜0.05),however,no similar results was found in the T/X genotype subgroup.As far as diabetes mellitus was concerned,the MIF-173 C allele carriers had higher morbility than the non-173C carriers(P＜0.05),regardless of the PPARγC1431 T variant.
(4)In CI patients,the MIF -173C carriers had a significant lower level of LDL-c than the non-173Ccarriers within the PPARγ1431CC genotype subgroup,while the difference was magnified in the PPARγ1431 T/X subgroup,significant higher level of LDL-c、DBPand BMI was observed in -173 C carriers compared to non-173C carriers (P＜0.05).PPARγ1431T / MIF-173 C carriers in CH patients have significant higher level of BMI than 1431T/non-173C carriers.
Conclusions
(1)No definite conclusion could be reached regarding the involvement of the -173G/C polymorphism of MIF in stroke,whereas PPARγC 1431T polymorphism might contribute to an increased risk of stroke among Chinese Han population of Hunan area.
(2)The MIF -173C allele might have a significant correlation to higher BMI levels in CI patients.The C1431T.polymorphism of PPARγmight be implicated in the lipid pathways and glyco-metabolism.
(3)PPARγC1431T and MIF-173G/C polymorphisms have a possible interaction in their effects on the presence of serum lipid concentrations,blood pressure and BMI.The association of MIF -173G/C genotype to them seems to be magnified to the synergistic effect of PPARγ1431C-＞T variant,which may result in a possible effect on stroke risk.
(1)探讨中国湖南汉族人群中MIF基因-173G/C多态性和PPARγ基因C1431T多态性及其交互作用与脑卒中的关系。
(2)探讨中国湖南汉族人群中MIF基因-173G/C多态性和PPARγ基因C1431T多态性及其交互作用与血脂、血压、血糖的关系。
方法:采用PCR-RFLP技术检测和DNA测序技术验证298例脑梗死患者、162例脑出血患者和203例对照者MIF基因-173G/C和PPARγ基因C1431T 2个位点多态性分布,同时检测研究对象的血脂、血压、血糖、BMI及IMT水平,以上所得数据采用SPSS13.0进行数据分析。
结果:
(1)中国湖南地区汉族人群存在MIF-173G/C、PPARγC1431T多态性,正常对照组中等位基因频率分别是G/C 0.793/0.207,C/T0.798/0.202。脑梗死组、脑出血组MIF-173G/C基因型和等位基因分布频率与对照组一致(P＞0.05),而PPARγT/X基因型频率和T等位基因频率均显著高于对照组(P＜0.05),这种差异在合并糖尿病和高血压病患者中尤为明显。
(2)脑梗死组MIF—173 C/X基因型BMI水平显著高于-173GG纯合子(P＜0.05)。脑梗死组PPARγ1431T/X基因型与CC纯合子相比,FBS及LDL-c水平显著升高,HDL-c水平显著降低(P＜0.05);脑出血组T等位基因携带者TG水平显著高于CC纯合子(P＜0.05)。
(3)“PPARγ1431T/X”亚组中,“MIF—173C/X”基因型脑卒中的发生率显著高于“MIF—173GG”基因型(P＜0.05);脑梗死组“PPARγ1431 T/X”与“MIF—173 C/X”联合变异患高血压的发病风险较其它各联合基因型显著升高(P＜0.05)。脑出血组仅在“PPARγ1431 CC”亚型中,“MIF—173C/X”基因型较“MIF—173GG”基因型患高血压的风险显著增高(P＜0.05)。无论“PPARγ1431T/X”变异存在与否,“MIF—173C/X”基因型较“MIF—173GG”基因型患糖尿病的风险均显著增高(P＜0.05)。
(4)脑梗死“PPARγ1431CC”基因型中,“MIF—173C/X”基因型LDL-c水平显著低于“MIF-173 GG”纯合子(P＜0.05);在“1431T/X”基因型中,“MIF—173C/X”基因型LDL-c、舒张压、BMI水平均显著高于“MIF-173 GG”纯合子(P＜0.05).脑出血“PPARγ1431 T/X”基因型中,“MIF—173C/X”基因型BMI水平显著高于“MIF—173GG”纯合子(P＜0.05)。
结论
(1)MIF-173G/C多态性可能与中国湖南汉族人脑卒中发生无关,而PPARγC1431T多态性可能与之相关。
(2)MIF-173 C等位基因可能与脑梗死患者较高的BMI水平有关,PPARγC1431T多态性可能参与了血脂、血糖代谢。
(3)PPARγC1431T和MIF-173G/C多态性对血脂、血压、BMI水平可能存在交互作用,继而影响脑卒中的发生。
Objectives Epidemiologic studies have shown that serum level of both MIF and PPARγare implicated in several physiologic pathways such as hypertension,lipid metabolism,severity of insulin resistance, inflammatory reaction,and atherosclerosis,all of which are closely related to the pathogenesis of stroke.MIF and PPARγgene exhibit genetically determined structural polymorphisms.Until now,several polymerphisms, i.e.-173G/C,+254(T/C)and +656(C/G)for MIF,Pro12Ala and C1431T for PPARγ,respectively,have been identified.The aim of the present study was to investigate possible effects of MIF-173G/C and PPARγC1431T polymorphisms as well as the interaction between the two tested polymorphisms on the presence of stroke,hypertension,and serum lipid levels in Chinese Han population of Hunan area.
Methods A total of 203 healthy individuals,298 patients with with cerebral infarction(CI)and 162 patients with primary cerebral hemorrhage(CH)of Chinese origin were were recruited in this study.The genotypes for the two tested SNPs were detected by polymerase chain reaction-restrictive fragment length polymorphism(PCR—RFLP)and DNA sequence.Serum lipid concentrations were determined by enzymatic analytical chemistry.
Results
(1)-173G/C of MIF and C1431T of PPARγpolymorphisms exist in Chinese people of Hunan area,with the allele frequencies 0.793/0.207for—173G/C and 0.798/0.202 for 1431 C/T,respectively.No significant differences were observed in genotypes and allele frequencies between stroke patients and controls for MIF-173G/C polymorphism(P＞0.05).As to PPARγC1431T polymorphism,significant higher frequencies of T allele and T/X genotype were confirmed in stroke patients with respect to the control subjects(P＜0.05),especially in patients with hypertention and diabetes mellitus.
(2)The MIF-173C allele carriers in CI patients have significant higher level of BMI than-173GG homozygosis(P＜0.05).Compared to the PPARγ1431CC homozygosis,T allele carriers in CI patients have significant higher levels of FBS and LDL-c while low level of HDL-c; T allele carriers in CH subjects only have significantly higher level of TG(P＜0.05).
(3)The combined effects of these two genes on stroke risk were examined by subgroup analyses.The result indicated that there exhibited no significant difference between MIF-173 C and non-173C carriers in the incidence of stroke within the PPARγ1431CC genotype subgroup, but the difference appeared within the 1431T/X genotype subgroup, that is to say MIF-173 C allele carriers had a higher risk of stroke than the non-173C carriers(P＜0.05).The combination mutations of PPARγ1431 C-＞T and MIF -173G-＞C have the highest risk of hypertention in CI group(P＜0.05).The MIF -173C carriers in CH patients had a higher incidence of hypertention than the non-173Ccarriers within the PPARγCC genotype subgroup(P＜0.05),however,no similar results was found in the T/X genotype subgroup.As far as diabetes mellitus was concerned,the MIF-173 C allele carriers had higher morbility than the non-173C carriers(P＜0.05),regardless of the PPARγC1431 T variant.
(4)In CI patients,the MIF -173C carriers had a significant lower level of LDL-c than the non-173Ccarriers within the PPARγ1431CC genotype subgroup,while the difference was magnified in the PPARγ1431 T/X subgroup,significant higher level of LDL-c、DBPand BMI was observed in -173 C carriers compared to non-173C carriers (P＜0.05).PPARγ1431T / MIF-173 C carriers in CH patients have significant higher level of BMI than 1431T/non-173C carriers.
Conclusions
(1)No definite conclusion could be reached regarding the involvement of the -173G/C polymorphism of MIF in stroke,whereas PPARγC 1431T polymorphism might contribute to an increased risk of stroke among Chinese Han population of Hunan area.
(2)The MIF -173C allele might have a significant correlation to higher BMI levels in CI patients.The C1431T.polymorphism of PPARγmight be implicated in the lipid pathways and glyco-metabolism.
(3)PPARγC1431T and MIF-173G/C polymorphisms have a possible interaction in their effects on the presence of serum lipid concentrations,blood pressure and BMI.The association of MIF -173G/C genotype to them seems to be magnified to the synergistic effect of PPARγ1431C-＞T variant,which may result in a possible effect on stroke risk.
引文
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