hsl外显子4-4A/G多态性与遵义地区汉族人群2型糖尿病的相关性研究
摘要
目的:进一步研究遵义地区人群激素敏感脂肪酶(HSL)基因第4外显子多态性与2型糖尿病的关系,为上述疾病的发病机理和临床治疗补充相关理论依据。
方法:采用两种实验设计,收集357例2型糖尿病患者和268例正常人血凝块各3毫升,碱裂解法提取血液细胞DNA;运用聚合酶链反应(PCR)扩增hsl第4外显子;结合单链构象多态性(SSCP)技术与RFLP技术对hsl第4外显子多态性进行进一步检测;实验结果进行统计学分析。
结果:
1.进一步验证了hsl第4外显子在遵义地区人群中具有多态分布。
2.所选样本基因型频率经Hardy-Weinburg遗传平衡定律检验达到平衡,具有群体代表性。
3.hsl外显子4-4A/G位点,所有样本:T2DM组检出GG基因型者51人,基因型频率为11.4%;AG基因型者157人,基因型频率为42.7%;AA基因型者149人,基因型频率为45.9%;对照组中,GG基因型者检出16人,基因型频率5.9%;AG基因型检出119人,基因型频率为44.3%;AA基因型检出133人,基因型频率为49.6%。随机病例-对照样本:T2DM组检出GG基因型者41人,基因型频率为13.5%; AG基因型者136人,基因型频率为44.2%;AA基因型者130人,基因型频率为42.3%;对照组中,GG基因型者检出10人,基因型频率4.7%;AG基因型检出98人,基因型频率为44.9%;AA基因型检出110人,基因型频率为50.4%。两组间三种基因型和两种等位基因的分布均存在显著性差异(P＜0.05);且GG基因型者占总人数的比列两组间比较差异显著(χ~2=9.027,P＜0.05和χ~2=8.46,P＜0.005); T2DM组人群GG基因型比例较高。
4.在病例和家系对照组中,GG基因型者检出率分别为10人和6人,AG基因型者检出均为21人,AA基因型者检出率分别为19人和23人。结果无统计学差异(χ~2=1.381, P＞0.05)。
5.将具有高脂血症者基因型和血脂正常组比较,经χ~2检验,两组基因型频率(χ~2=9.188, P＜0.05)和等位基因频率(χ~2=4.996,P＜0.05)差异显著,说明两组基因型和等位基因分布不同;且GG基因型人数占总人数的比例在高脂血症者和血脂正常两组间比较差异显著,高脂血症者组人群GG基因型比例较高(χ~2=7.129,P＜0.05)。
6.将腰臀比异常与腰臀比正常组基因型比较,经χ~2检验,两组基因型频率(χ~2=8.886,P＜0.05)和等位基因频率(χ~2=4.164,P＜0.05)差异显著,说明两组基因型和等位基因分布不同;且GG基因型人数占总人数的比例在腰臀比异常与腰臀比正常两组间比较差异显著,腰臀比异常组人群GG基因型比例较高(χ~2=7.523,P＜0.05)。
结论:
1.遵义地区汉族人群hsl外显子4具有多态性分布。
2.GG基因型是遵义地区汉族人群T2DM的遗传易感基因型。
3.GG基因型和携带有等位基因G者可能是高脂血症、腹部脂肪堆积的一个危险因素。
Objective: To investigate the relationship between the polymorphism hsl exon4 and type 2 diabetes mellitus in Han population of Zun Yi District. Our arms is to supplement the evidence for the pathogenesis of T2DM.
Methods: Samples including in 268 health persons and 368 type 2 diabetes were chosen, all of above are Han population of Zun Yi District. Clinical data were collected from hospital. Blood clot was collected to detect hsl .DNA was extracted from nucleated cell with alkaline. Design special primer to amplify hsl exon4 by PCR. Then the product of PCR was used to detect polymorphisms by SSCP and RFLP. SPSS16.0 was used to analyze.
Results:
1.Multi-state distributions were found in the exon4 of the hsl in the Zun Yi District infurther.
2.Hardy-Weinberg inherit equilibrium laws examination result showed that each genotypefrequency attains heredity balance and have a community representative.
3.There was a statistically significant difference in the genotype distribution of -4 A/G polymorphisms of hsl and allele variations among the all subjects and random - control group. The frequencies of G allele and GG genotype for T2DM patient were significantly higher than those of controls(GG:11.4%vs5.1%; G:χ~2=15.47,P＜0.05). Among all subject, the T2DM group genotype GG was 11.4%, AG was 42.7% and AA was 45.9% .Comparatively, among the control group, The genotype GG was 5.1%, AG was 44.3% and AA was 49.6%. Random - control group: the T2DM group genotype GG was 13.5%, AG was 44.2% and AA was 42.3%. Comparatively, among the control group, the genotype GG was 4.7%, AG was 44.9% and AA was 50.4%.
4.Among case-family group, the genotype GG was 20.0% and 12.0% respectively. The genotype AG were all 42.0%, AA was 38.0% and 46.0% respectively. Genotype distribution was no significant difference among the various groups (P＞0.05).
5.In stratified analysis on the basis of blood-fat, the frequencies of -4 A/G genotype and G allele for hyperlipoidemia group were significantly higher than those of controls(χ~2=9.188, P＜0.05,χ~2=4.996, P＜0.05).
6.In stratified analysis on the basis of WHR, the frequencies of -4 A/G genotype and G allele for abnormality WHR group were significantly higher than those of controls(χ~2=8.886,P＜0.05;χ~2=4.164,P＜0.05).
Conclusion:
1.Multi-state distributions was indicated in the exon4 of the hsl in Zun Yi District.
2.The genotype GG is the major of genotype for hereditary susceptibility of T2DM in ZunYi District.
3.The genotype GG and those carrying the G allele could be a risk factor for hyperlipoidemia and abdominal fat accumulation.
方法:采用两种实验设计,收集357例2型糖尿病患者和268例正常人血凝块各3毫升,碱裂解法提取血液细胞DNA;运用聚合酶链反应(PCR)扩增hsl第4外显子;结合单链构象多态性(SSCP)技术与RFLP技术对hsl第4外显子多态性进行进一步检测;实验结果进行统计学分析。
结果:
1.进一步验证了hsl第4外显子在遵义地区人群中具有多态分布。
2.所选样本基因型频率经Hardy-Weinburg遗传平衡定律检验达到平衡,具有群体代表性。
3.hsl外显子4-4A/G位点,所有样本:T2DM组检出GG基因型者51人,基因型频率为11.4%;AG基因型者157人,基因型频率为42.7%;AA基因型者149人,基因型频率为45.9%;对照组中,GG基因型者检出16人,基因型频率5.9%;AG基因型检出119人,基因型频率为44.3%;AA基因型检出133人,基因型频率为49.6%。随机病例-对照样本:T2DM组检出GG基因型者41人,基因型频率为13.5%; AG基因型者136人,基因型频率为44.2%;AA基因型者130人,基因型频率为42.3%;对照组中,GG基因型者检出10人,基因型频率4.7%;AG基因型检出98人,基因型频率为44.9%;AA基因型检出110人,基因型频率为50.4%。两组间三种基因型和两种等位基因的分布均存在显著性差异(P＜0.05);且GG基因型者占总人数的比列两组间比较差异显著(χ~2=9.027,P＜0.05和χ~2=8.46,P＜0.005); T2DM组人群GG基因型比例较高。
4.在病例和家系对照组中,GG基因型者检出率分别为10人和6人,AG基因型者检出均为21人,AA基因型者检出率分别为19人和23人。结果无统计学差异(χ~2=1.381, P＞0.05)。
5.将具有高脂血症者基因型和血脂正常组比较,经χ~2检验,两组基因型频率(χ~2=9.188, P＜0.05)和等位基因频率(χ~2=4.996,P＜0.05)差异显著,说明两组基因型和等位基因分布不同;且GG基因型人数占总人数的比例在高脂血症者和血脂正常两组间比较差异显著,高脂血症者组人群GG基因型比例较高(χ~2=7.129,P＜0.05)。
6.将腰臀比异常与腰臀比正常组基因型比较,经χ~2检验,两组基因型频率(χ~2=8.886,P＜0.05)和等位基因频率(χ~2=4.164,P＜0.05)差异显著,说明两组基因型和等位基因分布不同;且GG基因型人数占总人数的比例在腰臀比异常与腰臀比正常两组间比较差异显著,腰臀比异常组人群GG基因型比例较高(χ~2=7.523,P＜0.05)。
结论:
1.遵义地区汉族人群hsl外显子4具有多态性分布。
2.GG基因型是遵义地区汉族人群T2DM的遗传易感基因型。
3.GG基因型和携带有等位基因G者可能是高脂血症、腹部脂肪堆积的一个危险因素。
Objective: To investigate the relationship between the polymorphism hsl exon4 and type 2 diabetes mellitus in Han population of Zun Yi District. Our arms is to supplement the evidence for the pathogenesis of T2DM.
Methods: Samples including in 268 health persons and 368 type 2 diabetes were chosen, all of above are Han population of Zun Yi District. Clinical data were collected from hospital. Blood clot was collected to detect hsl .DNA was extracted from nucleated cell with alkaline. Design special primer to amplify hsl exon4 by PCR. Then the product of PCR was used to detect polymorphisms by SSCP and RFLP. SPSS16.0 was used to analyze.
Results:
1.Multi-state distributions were found in the exon4 of the hsl in the Zun Yi District infurther.
2.Hardy-Weinberg inherit equilibrium laws examination result showed that each genotypefrequency attains heredity balance and have a community representative.
3.There was a statistically significant difference in the genotype distribution of -4 A/G polymorphisms of hsl and allele variations among the all subjects and random - control group. The frequencies of G allele and GG genotype for T2DM patient were significantly higher than those of controls(GG:11.4%vs5.1%; G:χ~2=15.47,P＜0.05). Among all subject, the T2DM group genotype GG was 11.4%, AG was 42.7% and AA was 45.9% .Comparatively, among the control group, The genotype GG was 5.1%, AG was 44.3% and AA was 49.6%. Random - control group: the T2DM group genotype GG was 13.5%, AG was 44.2% and AA was 42.3%. Comparatively, among the control group, the genotype GG was 4.7%, AG was 44.9% and AA was 50.4%.
4.Among case-family group, the genotype GG was 20.0% and 12.0% respectively. The genotype AG were all 42.0%, AA was 38.0% and 46.0% respectively. Genotype distribution was no significant difference among the various groups (P＞0.05).
5.In stratified analysis on the basis of blood-fat, the frequencies of -4 A/G genotype and G allele for hyperlipoidemia group were significantly higher than those of controls(χ~2=9.188, P＜0.05,χ~2=4.996, P＜0.05).
6.In stratified analysis on the basis of WHR, the frequencies of -4 A/G genotype and G allele for abnormality WHR group were significantly higher than those of controls(χ~2=8.886,P＜0.05;χ~2=4.164,P＜0.05).
Conclusion:
1.Multi-state distributions was indicated in the exon4 of the hsl in Zun Yi District.
2.The genotype GG is the major of genotype for hereditary susceptibility of T2DM in ZunYi District.
3.The genotype GG and those carrying the G allele could be a risk factor for hyperlipoidemia and abdominal fat accumulation.
引文
[1] Zimmet P: Globalization, coca-colonization and the chronic disease epidemic: can the doomsday scenario be averted? J Intern Med 247:301-310,2000
[2] Pedersen O: Genetics of insulin resistance. Exp Clin Endocrinol Diab107:113-118, 1999
[3] Langin D, Holm C, Lafontan M: Adipocyte hormone-sensitive lipase: an important regulator of lipid metabolism. Proc Nutr Soc 55:93-109, 1996
[4] Boden G, Chen X. Effects of on glucose uptake and utilization in patients with non-insulin-dependent diabetes [J].J Clinic Invest, 1995,96:1261
[5] Boden G et al. Mechanisms of fatty acid-induced inhibition of glucose uptake [J]Clinic Invest, 1994,93:2348
[6] Levitt, R. C, Z. Liu, N. Noun, D. A. Meyers, B. Brandriff, and H. M. lipase (LIPE) to chromosome 19q13.1-q13.2. Cytogenet. Cell. Genet. 69: 211-214
[7] Shimada, F, H. Makino, N. Hashimoto, H. Iwaoka, M. Taira, O.Nozaki, A. Kanatsuka, C. Holm, D. Langin, and Y. Saito. 1996. Detection of an amino acid polymorphism in hormone-sensitive lipase in Japanese subjects. Metabolism. 45: 862-864
[8] Levitt, R. C, A E. Jedlicka, and N. Nouri. 1992. Dinucleotide repeat polymorphism at the hormone sensitive lipase (LIPE) locis Hum. Mol. Genet. 1: 139
[9] Talmud, PJ, J. Palmen, and M. Walker. 1998. Identification of genetic variation in the human hormone-sensitive lipase gene and5'sequences: homology of 5'sequences with mouse promoter and identification of potential regulatory elements. Biochem. Biophys Res Commun. 252: 661-668
[10] Klannemark, M. M,Orho. D,Langin. H,Laurell, C. Holm, S. Reynisdottir,P. Arner, and L. Groop. 1998. The putative role of the hormone-sensitive lipase gene in the pathogenesis of type Ⅱ diabetes mellitus and abdominal obesity. Diabetologia. 41: 1516-1522
[11] Magre, J., H. Laurell, C. Fizames, P. J. Antoine, C. Dib, C. Vigouroux,C. Bourut, J. Capeau, J. Weissenbach, and D. Langin. 1998. Human hormone-sensitive lipase: genetic mapping, identification of a new dinucleotide repeat, and association with obesity and NIDDM. Diabetes.47: 284-286
[12]王小卫等《用碱裂解法提取人血凝块中基因组DNA》西安交大学报(医学版)2007年10月第28卷第5期
[13][美]J.萨姆布鲁克著,黄培堂主译《分子克隆实验指南》精编版化学工业出版社
[14]Boden, G. Role of fatty acids in the pathogenesis of insulin resistance and NEDDM. Diabetes. 1997. 46: 3-10
[15]Boden G, Chen X. Effects of on glucose uptake and utilization in patients with non-insulin-dependent diabetes [J] .J Clin Invest, 1995,96:1261
[16]Stumvoll, M., and S. Jacob. 1999. Multiple sites of insulin resistance: muscle, liver and adipose tissue. Exp. Clin. Endocrinol. Diabetes, 107: 107-110
[17]Groop, L. C, R. C. Bonadonna, S. DelPrato, K. Ratheiser, K. Zyck, E.Ferrannini, and R. A. DeFronzo. 1989. Glucose and free fatty acid metabolism in non-insulin-dependent diabetes mellitus. Evidence for multiple sites of insulin resistance. J. Clin. Invest. 84:205-213
[18]Campbell, P. J., M. G. Carlson, J. O. Hill, and N. Nurjhan. 1992. Regulation of free fatty acid metabolism by insulin in humans: role of lipolysis and reesterification. Am. J. Physiol. 263: E1063-E1068
[1] Boden G, Chen X. Effects of on glucose uptake and utilization in patients with non-insulin-dependent diabetes [J] Clin Invest, 1995,96:1261
[2] Boden G et al. Mechanisms of fatty acid-induced inhibition of glucose uptake [J]Clin Invest, 1994,93:2348
[3] Levitt, R. C, Z. Liu, N. Nouri, D. A. Meyers, B. Brandriff, and H. M. Lipase (LIPE) to chromosome 19q13.1-q13.2. Cytogenet. Cell. Genet. 69: 211-214
[4] Langin D, Laurell H, Hoist LS, et al.Gene organization and primary structure of human hormone-sensitive lipase: possible significance of a sequence homology with a lipase of Moraxellata144,an Antarctic bacterium.[J]Pro Nacl Acad Scil993,4897-4901
[5] Mulder H,Holst LS,Svensson H,et al. Hormone-sensitive lipase, the rate-limiting enzyme in triglyceride hydrolysis is expressed and active in β-cell.[J] Diabetes, 1999,48:228-232
[6] Holm C,T.Osterlund,H.Laurell,et al. Molecular mechanisms regulating hormone sensitive lipase and lipolysis.[J]Annu Rev Nutr,2000,20:365-393
[7] Grober J,Laurell H,Blaise R, et al. Characterization of the promoter of human hormor.e-sensitive lipase.[J]Biochem, 1997,328:453-461
[8] Lindvall H,Nevsten P,Strom K, et al. A novel hormone-sensitive lipase isoform expressed in pancreatic β cells.[J] Biochem,2004,279:3828-3836
[9] Hoist LS, Langin D,M|ilder H, et al. Molecular cloning, genomic organization, and expression of a testicular isoform of hormone-sensitive lipase.[J]Genomics,1996,35: 441-447
[10] Johan Hoffstedt, et al. A Common Hormone-Sensitive Lipase i6 Gene Polymorphism Is Associated With Decreased Human Adipocyte Lipolytic Function [J] Diabetes vol. 50, October, 2001,2410-2413
[11] Michael Stumvoll, et al. Two novel prevalent polymorphisms in the hormone-sensitive lipase gene have no effect on insulin sensitivity of lipolysis and glucose disposal [J] Journal of Lipid Research Volume 42, 2001,1782-1788.
[12]Pihlajamaki J,Balve R,Kavjalainen L, et al. The hormone-sensitive lipase gene in familial combines hyperlipidemia and insulin resistance.[J] Eur J Clin Invest,2001,31(4):302-308
[13]Shimada F,Makino H,Hashimoto N, et al. Detection of an amino acid polymorphism in hormone-sensitive lipase in Japanese subject.[J] Metabolism,1996,45(7):862-864
[14]Talmud PJ,Palmen J,Nicaud B, et al. Association of the hormone-sensitive lipase 60C> G variant with fasting insulin levels in healthy young men.[J]Nutr Metab Cardiovasc Dis,2002,12(4):173-177
[15]Gerich, J. E. 1998. The genetic basis of type 2 diabetes mellitus: impaired insulin secretion versus impaired insulin sensitivity. Endocr.Rev. 19: 491-503
[16]Boden, G. Role of fatty acids in the pathogenesis of insulin resistance and NIDDM. Diabetes. 1997. 46: 3-10
[17]Stumvoll, M., and S. Jacob. 1999. Multiple sites of insulin resistance: muscle, liver and adipose tissue. Exp. Clin. Endocrinol. Diabetes, 107: 107-110
[18]Groop, L. C, R. C. Bonadonna, S. DelPrato, K. Ratheiser, K. Zyck, E.Ferrannini, and R. A. DeFronzo. 1989. Glucose and free fatty acid metabolism in non-insulin-dependent diabetes mellitus. Evidence for multiple sites of insulin resistance. J. Clin. Invest. 84: 205-213
[19]Campbell, P. J., M. G. Carlson, and N. Nurjhan. 1994. Fat metabolism in human obesity. Am. J. Physiol. 266: E600-E605
[20]Groop, L. C, R. C. Bonadonna, D. C. Simonson, A. S. Petrides, M.Shank, and R. A. DeFronzo. 1992. Effect of insulin on oxidative and no noxidative pathways of free fatty acid metabolism in human obesity. Am. J. Physiol. 263: E79-E84
[21]Johan W.E. Jocken, Ellen E. Blaak, Blunted P-adrenoceptor-mediated fat oxidation in overweight subjects: a role for the hormone-sensitive lipase gene Metabolism Clinical and Experimental 57 (2008) 326-332
[2] Pedersen O: Genetics of insulin resistance. Exp Clin Endocrinol Diab107:113-118, 1999
[3] Langin D, Holm C, Lafontan M: Adipocyte hormone-sensitive lipase: an important regulator of lipid metabolism. Proc Nutr Soc 55:93-109, 1996
[4] Boden G, Chen X. Effects of on glucose uptake and utilization in patients with non-insulin-dependent diabetes [J].J Clinic Invest, 1995,96:1261
[5] Boden G et al. Mechanisms of fatty acid-induced inhibition of glucose uptake [J]Clinic Invest, 1994,93:2348
[6] Levitt, R. C, Z. Liu, N. Noun, D. A. Meyers, B. Brandriff, and H. M. lipase (LIPE) to chromosome 19q13.1-q13.2. Cytogenet. Cell. Genet. 69: 211-214
[7] Shimada, F, H. Makino, N. Hashimoto, H. Iwaoka, M. Taira, O.Nozaki, A. Kanatsuka, C. Holm, D. Langin, and Y. Saito. 1996. Detection of an amino acid polymorphism in hormone-sensitive lipase in Japanese subjects. Metabolism. 45: 862-864
[8] Levitt, R. C, A E. Jedlicka, and N. Nouri. 1992. Dinucleotide repeat polymorphism at the hormone sensitive lipase (LIPE) locis Hum. Mol. Genet. 1: 139
[9] Talmud, PJ, J. Palmen, and M. Walker. 1998. Identification of genetic variation in the human hormone-sensitive lipase gene and5'sequences: homology of 5'sequences with mouse promoter and identification of potential regulatory elements. Biochem. Biophys Res Commun. 252: 661-668
[10] Klannemark, M. M,Orho. D,Langin. H,Laurell, C. Holm, S. Reynisdottir,P. Arner, and L. Groop. 1998. The putative role of the hormone-sensitive lipase gene in the pathogenesis of type Ⅱ diabetes mellitus and abdominal obesity. Diabetologia. 41: 1516-1522
[11] Magre, J., H. Laurell, C. Fizames, P. J. Antoine, C. Dib, C. Vigouroux,C. Bourut, J. Capeau, J. Weissenbach, and D. Langin. 1998. Human hormone-sensitive lipase: genetic mapping, identification of a new dinucleotide repeat, and association with obesity and NIDDM. Diabetes.47: 284-286
[12]王小卫等《用碱裂解法提取人血凝块中基因组DNA》西安交大学报(医学版)2007年10月第28卷第5期
[13][美]J.萨姆布鲁克著,黄培堂主译《分子克隆实验指南》精编版化学工业出版社
[14]Boden, G. Role of fatty acids in the pathogenesis of insulin resistance and NEDDM. Diabetes. 1997. 46: 3-10
[15]Boden G, Chen X. Effects of on glucose uptake and utilization in patients with non-insulin-dependent diabetes [J] .J Clin Invest, 1995,96:1261
[16]Stumvoll, M., and S. Jacob. 1999. Multiple sites of insulin resistance: muscle, liver and adipose tissue. Exp. Clin. Endocrinol. Diabetes, 107: 107-110
[17]Groop, L. C, R. C. Bonadonna, S. DelPrato, K. Ratheiser, K. Zyck, E.Ferrannini, and R. A. DeFronzo. 1989. Glucose and free fatty acid metabolism in non-insulin-dependent diabetes mellitus. Evidence for multiple sites of insulin resistance. J. Clin. Invest. 84:205-213
[18]Campbell, P. J., M. G. Carlson, J. O. Hill, and N. Nurjhan. 1992. Regulation of free fatty acid metabolism by insulin in humans: role of lipolysis and reesterification. Am. J. Physiol. 263: E1063-E1068
[1] Boden G, Chen X. Effects of on glucose uptake and utilization in patients with non-insulin-dependent diabetes [J] Clin Invest, 1995,96:1261
[2] Boden G et al. Mechanisms of fatty acid-induced inhibition of glucose uptake [J]Clin Invest, 1994,93:2348
[3] Levitt, R. C, Z. Liu, N. Nouri, D. A. Meyers, B. Brandriff, and H. M. Lipase (LIPE) to chromosome 19q13.1-q13.2. Cytogenet. Cell. Genet. 69: 211-214
[4] Langin D, Laurell H, Hoist LS, et al.Gene organization and primary structure of human hormone-sensitive lipase: possible significance of a sequence homology with a lipase of Moraxellata144,an Antarctic bacterium.[J]Pro Nacl Acad Scil993,4897-4901
[5] Mulder H,Holst LS,Svensson H,et al. Hormone-sensitive lipase, the rate-limiting enzyme in triglyceride hydrolysis is expressed and active in β-cell.[J] Diabetes, 1999,48:228-232
[6] Holm C,T.Osterlund,H.Laurell,et al. Molecular mechanisms regulating hormone sensitive lipase and lipolysis.[J]Annu Rev Nutr,2000,20:365-393
[7] Grober J,Laurell H,Blaise R, et al. Characterization of the promoter of human hormor.e-sensitive lipase.[J]Biochem, 1997,328:453-461
[8] Lindvall H,Nevsten P,Strom K, et al. A novel hormone-sensitive lipase isoform expressed in pancreatic β cells.[J] Biochem,2004,279:3828-3836
[9] Hoist LS, Langin D,M|ilder H, et al. Molecular cloning, genomic organization, and expression of a testicular isoform of hormone-sensitive lipase.[J]Genomics,1996,35: 441-447
[10] Johan Hoffstedt, et al. A Common Hormone-Sensitive Lipase i6 Gene Polymorphism Is Associated With Decreased Human Adipocyte Lipolytic Function [J] Diabetes vol. 50, October, 2001,2410-2413
[11] Michael Stumvoll, et al. Two novel prevalent polymorphisms in the hormone-sensitive lipase gene have no effect on insulin sensitivity of lipolysis and glucose disposal [J] Journal of Lipid Research Volume 42, 2001,1782-1788.
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