Wolford J K, Hanson R L, Kobes S, Bogardus C, Prochazka M
Clinical Diabetes and Nutrition Section, Phoenix Epidemiology and Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, 4212 North 16th Street, Phoenix, AZ 85016, USA. jwolford@exchange,nih.gov
Mol Genet Metab. 2001 May;73(1):97-103. doi: 10.1006/mgme.2001.3167.
The KCNJ9 gene encodes a G-protein-coupled inwardly rectifying potassium channel and is located within a region on human chromosome 1 that has been linked with type 2 diabetes mellitus in Pima Indians and Caucasians. To assess the potential contribution of genetic alterations within KCNJ9 to diabetes susceptibility in the Pimas, we have genotyped 11 single nucleotide polymorphisms (SNPs) in 50 Pimas with diabetes and 50 Pimas over the age of 45 without diabetes and in 51 sib pairs, discordant for the disease, who were characterized by decreased allele sharing at the chromosomal location of the maximum LOD score. We detected three SNP clusters exhibiting distinct linkage disequilibria. Polymorphisms in intron 2, exon 3, and the 3'-UTR were in statistically significant linkage disequilibrium with diabetes in the case-control group (P = 0.006), but not the sibling pairs (P = 0.097). A weak association with diabetes was also found in the original linkage set comprising 1150 Pimas (odds ratio = 0.64/P = 0.079 for a dominant model and OR = 0.67/P = 0.005 for a recessive model). However, no effect on linkage was detected following adjustment for one of the most strongly associated SNPs in the entire original linkage set. Our results indicate that variants in KCNJ9 are associated with diabetes in Pimas but do not account for the linkage of 1q with diabetes in this population.
KCNJ9基因编码一种G蛋白偶联内向整流钾通道，位于人类1号染色体上的一个区域，该区域在皮马印第安人和高加索人中与2型糖尿病相关。为了评估KCNJ9基因内基因改变对皮马人糖尿病易感性的潜在影响，我们对50名患有糖尿病的皮马人、50名45岁以上无糖尿病的皮马人以及51对患病情不一致的同胞对进行了11个单核苷酸多态性（SNP）的基因分型，这些同胞对在最大LOD评分的染色体位置上等位基因共享减少。我们检测到三个表现出不同连锁不平衡的SNP簇。在病例对照组中，内含子2、外显子3和3'-UTR中的多态性与糖尿病存在统计学显著的连锁不平衡（P = 0.006），但在同胞对中则不然（P = 0.097）。在最初包含1150名皮马人的连锁组中也发现了与糖尿病的弱关联（显性模型的优势比 = 0.64/P = 0.079，隐性模型的OR = 0.67/P = 0.005）。然而，在对整个原始连锁组中最强烈关联的一个SNP进行校正后，未检测到对连锁的影响。我们的结果表明，KCNJ9基因的变异与皮马人的糖尿病相关，但不能解释该人群中1q与糖尿病的连锁关系。
