综述

糖尿病肾病遗传学研究进展

展开
  • 1.上海中医药大学附属曙光医院内分泌科, 糖尿病研究所, 上海市中医临床重点实验室, 上海 201203 2.上海交通大学Bio-X研究院, 上海 200030

收稿日期: 2012-05-23

  修回日期: 2012-08-21

  网络出版日期: 2012-12-25

基金资助

上海市教育委员会重点学科(第五期)建设项目(编号:J50307), 浦东新区卫生系统重点学科群建设(编号:PWZxkq2010-04), 上海市中医临床重点实验室项目(C10dz2220200), 上海浦江人才项目(编号:11PJ1408900)和上海东方学者项目(2010)资助

Advances of genetics in diabetic nephropathy

Expand
  • 1. Diabetes Research Institute, Department of Endocrinology, Shanghai Key Laboratory of Traditional Chinese Clinical Medice, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China 2. Bio-X Institutes Shanghai Jiao Tong University, Shanghai 200030, China

Received date: 2012-05-23

  Revised date: 2012-08-21

  Online published: 2012-12-25

摘要

糖尿病肾病是糖尿病最严重的慢性并发症之一, 不同种族的发病率分析和家族聚集性研究显示遗传因素是糖尿病肾病发生、发展的重要因素。文章从3个方面对糖尿病肾病的遗传学研究进展进行综述:“候选基因”的关联研究、连锁分析和全基因组关联研究。关联研究及荟萃分析显示一些候选基因与糖尿病肾病显著相关, 包括ACE、AGTPPARG等基因; 连锁分析及全基因组连锁分析发现多个糖尿病肾病的易感染色体位点; 随着高通量测序技术和芯片技术的发展, 全基因组关联研究已成为糖尿病肾病遗传学研究的重要途径。虽然遗传因素在糖尿病肾病发病中占据重要的位置, 但还不能完全解释糖尿病肾病的发病原因, 因为糖尿病肾病的发生还受环境因素的影响, 然而糖尿病肾病的遗传学研究可为糖尿病肾病发病机制研究以及药物治疗靶点研究提供一定的理论依据。

本文引用格式

李俊燕,谭英姿,冯国鄞,贺林,周里钢,陆灏 . 糖尿病肾病遗传学研究进展[J]. 遗传, 2012 , 34(12) : 1537 -1544 . DOI: 10.3724/SP.J.1005.2012.01537

Abstract

Diabetic nephropathy (DN) is one of the most serious chronic complications of diabetes mellitus. The observed incidence patterns in different ethnics and familial clustering have suggested that the genetic factor plays an important role in the development and progression of DN. This paper reviews the recent advances on genetics of DN, including candidate genes association studies, linkage studies and genome-wide association studies (GWASs). Candidate genes association studies and meta-analysis showed that a few candidate genes have been reproducibly associated with DN, such as ACE, AGT and PPARG genes. Linkage studies and genome-wide linkage studies have also identified susceptibility chromosomal loci. With the development of high-throughput sequencing and chip techniques, GWAS has become an important strategy to identify variants responsible for DN. The genetic factor has been the significant contribution to the pathobiology of DN. However, it is not the only cause of the pathobiology of DN, because the environment factor also influences the pathobiology of DN. Nonetheless, genetic studies may provide valuable information for the pathobiology of nephropathy and potential targets of its treatment.

参考文献

[1] Collins AJ, Foley RN, Herzog C, Chavers B, Gilbertson D, Ishani A, Kasiske B, Liu J, Mau LW, McBean M, Murray A, St Peter W, Guo H, Gustafson S, Li Q, Li S, Peng Y, Qiu Y, Roberts T, Skeans M, Snyder J, Solid C, Wang C, Weinhandl E, Zaun D, Arko C, Chen SC, Dalleska F, Daniels F, Dunning S, Ebben J, Frazier E, Hanzlik C, Johnson R, Sheets D, Wang X, Forrest B, Constantini E, Everson S, Eggers P, Agodoa L. Us renal data system 2010 annual data report. Am J Kidney Dis, 2011, 57(S1): A8, e1-526.
[2] Kanwar YS, Sun L, Xie P, Liu FY, Chen S. A glimpse of various pathogenetic mechanisms of diabetic nephropathy. Annu Rev Pathol, 2011, 6(1): 395-423.
[3] Quinn M, Angelico MC, Warram JH, Krolewski AS. Familial factors determine the development of diabetic nephropathy in patients with IDDM. Diabetologia, 1996, 39(8): 940-945.
[4] Harjutsalo V, Katoh S, Sarti C, Tajima N, Tuomilehto J. Population-based assessment of familial clustering of diabetic nephropathy in type 1 diabetes. Diabetes, 2004, 53(9): 2449-2454.
[5] Pettitt DJ, Saad MF, Bennett PH, Nelson RG, Knowler WC. Familial predisposition to renal disease in two generations of Pima Indians with type 2 (non-insulin-dependent) dia-betes mellitus. Diabetologia, 1990, 33(7): 438-443.
[6] Mooyaart AL, Valk EJ, van Es LA, Bruijn JA, de Heer E, Freedman BI, Dekkers OM, Baelde HJ. Genetic associations in diabetic nephropathy: A meta-analysis. Diabe-tologia, 2011, 54(3): 544-553.
[7] Wang FR, Fang QQ, Yu NL, Zhao DY, Zhang YM, Wang J, Wang Q, Zhou XF, Cao XJ, Fan XY. Association between genetic polymorphism of the angiotensin-converting en-zyme and diabetic nephropathy: A meta-analysis comprising 26, 580 subjects. J Renin Angiotensin Aldosterone Syst, 2012, 13(1): 161-174.
[8] Wang Y, Ng MCY, So WY, Tong PCY, Ma RCW, Chow CC, Cockram CS, Chan JCN. Prognostic effect of inser-tion/deletion polymorphism of the ace gene on renal and cardiovascular clinical outcomes in chinese patients with type 2 diabetes. Diabetes Care, 2005, 28(2): 348-354.
[9] So WY, Ma RC, Ozaki R, Tong PC, Ng MC, Ho CS, Lam CW, Chow CC, Chan WB, Kong AP, Chan JC. Angio-tensin-converting enzyme (ace) inhibition in type 2, dia-betic patients--interaction with ace insertion/deletion polymorphism. Kidney Int, 2006, 69(8): 1438-1443.
[10] 马青云. 糖尿病肾病遗传学研究现状. 中华糖尿病杂志, 2012, 4(1): 7-8.
[11] Freedman BI, Bowden DW, Rich SS, Xu J, Wagenknecht LE, Ziegler J, Hicks PJ, Langefeld CD. Genome-wide linkage scans for renal function and albuminuria in type 2 diabetes mellitus: The diabetes heart study. Diabet Med, 2008, 25(3): 268-276.
[12] Osterholm AM, He B, Pitkaniemi J, Albinsson L, Berg T, Sarti C, Tuomilehto J, Tryggvason K. Genome-wide scan for type 1 diabetic nephropathy in the finnish population reveals suggestive linkage to a single locus on chromo-some 3q. Kidney Int, 2007, 71(2): 140-145.
[13] Placha G, Poznik GD, Dunn J, Smiles A, Krolewski B, Glew T, Puppala S, Schneider J, Rogus JJ, Rich SS, Duggirala R, Warram JH, Krolewski AS. A genome-wide linkage scan for genes controlling variation in renal function estimated by serum cystatin c levels in extended families with type 2 diabetes. Diabetes, 2006, 55(12): 3358-3365.
[14] Schelling JR, Abboud HE, Nicholas SB, Pahl MV, Sedor JR, Adler SG, Arar NH, Bowden DW, Elston RC, Freed-man BI, Goddard KA, Guo X, Hanson RL, Ipp E, Iyengar SK, Jun G, Kao WH, Kasinath BS, Kimmel PL, Klag MJ, Knowler WC, Nelson RG, Parekh RS, Quade SR, Rich SS, Saad MF, Scavini M, Smith MW, Taylor K, Winkler CA, Zager PG, Shah VO. Genome-wide scan for estimated glomerular filtration rate in multi-ethnic diabetic populations: The family investigation of nephropathy and diabetes (find). Diabetes, 2008, 57(1): 235-243.
[15] Wessman M, Forsblom C, Kaunisto MA, Söderlund J, Ilonen J, Sallinen R, Hiekkalinna T, Parkkonen M, Max-well AP
文章导航

/