通过对俄罗斯1型糖尿病患者的关联研究，证实3号染色体q23-q24区域存在糖尿病肾病易感性位点。

Confirmation of a susceptibility locus for diabetic nephropathy on chromosome 3q23-q24 by association study in Russian type 1 diabetic patients.

作者信息

Chistiakov Dimitry A, Savost'anov Kirill V, Shestakova Marina V, Chugunova Lyudmila A, Samkhalova Minara Sh, Dedov Ivan I, Nosikov Valery V

机构信息

Laboratory of Aquatic Ecology, Katholieke Universiteit Leuven, Ch. de Beriotstraat 32, B-3000 Leuven, Belgium.

出版信息

Diabetes Res Clin Pract. 2004 Oct;66(1):79-86. doi: 10.1016/j.diabres.2004.02.011.

DOI:10.1016/j.diabres.2004.02.011

PMID:15364165

Abstract

Family-based studies and segregation analyses suggest that inherited factors play a significant role in susceptibility to diabetic nephropathy (DN). Moczulski et al. [Diabetes 47 (1998) 1164-1169] found a susceptibility locus for DN in type 1 diabetes covering a 20cM region on chromosome 3q, with a peak of linkage close to the angiotensin II type 1 receptor (AT1) gene. We examined eight polymorphic markers (D3S1512, D3S1550, D3S1557, D3S1744, D3S2326, D3S3599, D3S3694, and a (CA)(n) dinucleotide repeat polymorphism in the 3' flanking region of the AT1 gene) spanning about 6.2 megabases (Mb) in the region of maximal linkage with DN on chromosome 3q23-q24. The markers were used to genotype a total of 381 Russian type 1 diabetic subjects, 195 of whom had DN and 186 had no clinical nephropathy. Four of the markers tested, D3S1512, D3S1550, D3S2326, and D3S3599, showed an association with DN in type 1 diabetes mellitus. These markers are located within a 1.0Mb interval that starts about 4.4Mb centromeric to the AT1 gene. Thus, our results suggest the existence of the DN susceptibility locus previously described by Moczulski et al. on chromosome 3q.

摘要

基于家系的研究和分离分析表明，遗传因素在糖尿病肾病（DN）易感性中起重要作用。莫祖尔斯基等人[《糖尿病》47（1998）1164 - 1169]在1型糖尿病中发现了一个DN易感基因座，位于3号染色体q臂上一个20厘摩的区域，连锁峰值靠近血管紧张素II 1型受体（AT1）基因。我们检测了8个多态性标记（D3S1512、D3S1550、D3S1557、D3S1744、D3S2326、D3S3599、D3S3694以及AT1基因3'侧翼区域的一个（CA）（n）二核苷酸重复多态性），这些标记跨越3号染色体q23 - q24上与DN连锁最强区域约6.2兆碱基（Mb）。这些标记用于对总共381名俄罗斯1型糖尿病患者进行基因分型，其中195人患有DN，186人无临床肾病。所检测的4个标记，即D3S1512、D3S1550、D3S2326和D3S3599，在1型糖尿病中显示与DN相关。这些标记位于一个1.0Mb的区间内，该区间起始于距AT1基因着丝粒约4.4Mb处。因此，我们的结果提示莫祖尔斯基等人先前描述的位于3号染色体q臂上的DN易感基因座的存在。