Farook Vidya S, Hanson Robert L, Wolford Johanna K, Bogardus Clifton, Prochazka Michal
Clinical Diabetes and Nutrition Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85016, USA.
Diabetes. 2002 Nov;51(11):3342-6. doi: 10.2337/diabetes.51.11.3342.
The KCNJ10 gene is located within a region on chromosome 1q linked to type 2 diabetes in the Pima Indians and six other populations. We therefore investigated this gene as a potential type 2 diabetes candidate gene in Pima Indians. KCNJ10 consists of two exons, spans approximately 33 kb, and we identified eight single-nucleotide polymorphisms (SNPs), including one (SNP2) in the coding region leading to a Glu359Lys substitution. Association studies were carried out in a case-control group composed of 149 affected and 150 unaffected Pimas, and the linkage analysis was performed in a linkage set of 1,338 Pimas. SNP1 in the promoter and SNP2 in the intron, which were in a complete linkage disequilibrium, and SNP5 in the 3' untranslated region showed association with diabetes in the case-control group (P = 0.02 and P = 0.01, respectively). When genotyped in the linkage set, only the KCNJ10-SNP1 variant showed a modest association with type 2 diabetes (P = 0.01). KCNJ10-SNP1 is in a strong linkage disquilibrium with SNP14 of the adjacent KCNJ9 locus, which we previously found to be associated with type 2 diabetes. After adjustment for KCNJ10-SNP1, the original linkage score at this locus was marginally reduced from 3.1 to 2.9. We conclude that these variants in KCNJ10 are unlikely to be the cause of linkage of type 2 diabetes with 1q in Pima Indians.
KCNJ10基因位于1号染色体上与皮马印第安人及其他六个群体的2型糖尿病相关的区域内。因此，我们将该基因作为皮马印第安人中2型糖尿病的潜在候选基因进行了研究。KCNJ10由两个外显子组成，跨度约为33 kb，我们鉴定出了8个单核苷酸多态性（SNP），其中包括编码区的一个（SNP2），该突变导致Glu359Lys替换。在一个由149名患病皮马人和150名未患病皮马人组成的病例对照群体中进行了关联研究，并在1338名皮马人的连锁组中进行了连锁分析。启动子中的SNP1和内含子中的SNP2处于完全连锁不平衡状态，3'非翻译区的SNP5在病例对照群体中显示与糖尿病相关（P值分别为0.02和0.01）。在连锁组中进行基因分型时，只有KCNJ10 - SNP1变异与2型糖尿病存在适度关联（P = 0.01）。KCNJ10 - SNP1与相邻的KCNJ9基因座的SNP14处于强连锁不平衡状态，我们之前发现该基因座与2型糖尿病相关。在对KCNJ10 - SNP1进行校正后，该基因座的原始连锁分数从3.1略微降至2.9。我们得出结论，KCNJ10中的这些变异不太可能是皮马印第安人中2型糖尿病与1号染色体连锁的原因。
