Replication study for the association between four Loci identified by a genome-wide association study on European American subjects with type 1 diabetes and susceptibility to diabetic nephropathy in Japanese subjects with type 2 diabetes.
Replication study for the association between four Loci identified by a genome-wide association study on European American subjects with type 1 diabetes and susceptibility to diabetic nephropathy in Japanese subjects with type 2 diabetes.
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DOI：
10.2337/db10-0067
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发表时间：
2010-08
期刊：
影响因子：
7.7
通讯作者：
Nakamura Y
中科院分区：
文献类型：
--
作者：
Maeda S;Araki S;Babazono T;Toyoda M;Umezono T;Kawai K;Imanishi M;Uzu T;Watada H;Suzuki D;Kashiwagi A;Iwamoto Y;Kaku K;Kawamori R;Nakamura Y
糖尿病肾病的发病与糖尿病肾病的发病有密切关系。最近，糖尿病肾病的全基因组关联研究揭示了4个新的候选位点在欧洲1型糖尿病患者中。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系。我们在四个不同的基因座上对11个单核苷酸多态性（SNPs）进行了基因分型。（CPVL/CHN 2中的rs39059和rs39075，FRMD 3中的rs 1888747和rs 10868025，汽车中的rs739401和rs 451041，以及rs 1041466，rs 1411766，rs6492208，rs7989848，和rs 9521445）。在四个日本人群中，有六个SNPs与糖尿病肾病名义上相关（P < 0.05;研究1中的rs 451041;研究3中的rs39059和rs 1888747;研究1和4中的rs 1411766;以及研究4中的rs7989848和rs 9521445）;然而，在个体群体中校正多个测试误差后，没有观察到任何SNP的显著关联。然而，对所有四个人群获得的数据进行的荟萃分析显示，染色体13 q中的一个SNP（rs 1411766）与日本人群中的糖尿病肾病显著相关（标称P = 0.004，校正P = 0.04，比值比1.26 [95%CI = 1.07-1.47]）。我们的研究结果表明，rs 1411766位点可能是共同参与赋予1型或2型糖尿病患者在不同种族人群中的糖尿病肾病的易感性。
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.