Laboratory for Endocrinology and Metabolism, RIKEN Center for Genomic Medicine, Yokohama, Japan.
Diabetes. 2010 Aug;59(8):2075-9. doi: 10.2337/db10-0067. Epub 2010 May 11.
Genetic factors are believed to contribute to the development and progression of diabetic nephropathy. Recently, a genome-wide association study for diabetic nephropathy revealed four novel candidate loci in European American subjects with type 1 diabetes. In this study, we determined the association of the four loci with diabetic nephropathy in Japanese subjects with type 2 diabetes.
We genotyped 11 singlenucleotide polymorphisms (SNPs) in four distinct loci (rs39059 and rs39075 in the CPVL/CHN2, rs1888747 and rs10868025 in FRMD3, rs739401 and rs451041 in CARS, and rs1041466, rs1411766, rs6492208, rs7989848, and rs9521445 in a chromosome 13q locus) in four independent Japanese populations.
Six SNPs were nominally associated with diabetic nephropathy in one of the four Japanese populations (P < 0.05; rs451041 in study 1; rs39059 and rs1888747 in study 3; rs1411766 in studies 1 and 4; and rs7989848 and rs9521445 in study 4); however, no significant association was observed for any SNP after correction for multiple testing errors in the individual populations. Nevertheless, a meta-analysis performed for the data obtained from all four populations revealed that one SNP (rs1411766) in chromosome 13q was significantly associated with diabetic nephropathy in the Japanese populations (nominal P = 0.004, corrected P = 0.04, odds ratio 1.26 [95% CI = 1.07-1.47]).
Our results suggest that the rs1411766 locus may be commonly involved in conferring susceptibility to diabetic nephropathy among subjects with type 1 or type 2 diabetes across different ethnic groups.
遗传因素被认为与糖尿病肾病的发生和进展有关。最近，一项针对糖尿病肾病的全基因组关联研究在 1 型糖尿病的欧洲裔美国人中发现了四个新的候选位点。在这项研究中，我们确定了这四个位点与日本 2 型糖尿病患者糖尿病肾病的关联。
我们对四个不同位置的 11 个单核苷酸多态性（SNP）（CPVL/CHN2 中的 rs39059 和 rs39075、FRMD3 中的 rs1888747 和 rs10868025、CARS 中的 rs739401 和 rs451041 以及染色体 13q 位置的 rs1041466、rs1411766、rs6492208、rs7989848 和 rs9521445）在四个独立的日本人群中进行了基因分型。
六个 SNP 在四个日本人群中的一个人群中与糖尿病肾病呈名义相关（P < 0.05；研究 1 中的 rs451041；研究 3 中的 rs39059 和 rs1888747；研究 1 和 4 中的 rs1411766；以及研究 4 中的 rs7989848 和 rs9521445）；然而，在对各个人群中的多重测试错误进行校正后，没有观察到任何 SNP 的显著关联。然而，对来自四个群体的数据进行的荟萃分析显示，染色体 13q 上的一个 SNP（rs1411766）与日本人群中的糖尿病肾病显著相关（名义 P = 0.004，校正 P = 0.04，优势比 1.26 [95%CI = 1.07-1.47]）。
我们的结果表明，rs1411766 位点可能在不同种族的 1 型或 2 型糖尿病患者中共同参与糖尿病肾病易感性的赋予。
