Molecular Analysis of KCNJ10 on 1q as a Candidate Gene for Type 2 Diabetes in Pima Indians
- From the 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
Abstract
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 ∼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.
Footnotes
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Address correspondence and reprint requests to Vidya S. Farook, Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 4212 North 16th St., Phoenix, AZ 85016. E-mail: vfarook{at}mail.nih.gov.
Received for publication12 March 2002 and accepted in revised form 2 August 2002.
Additional information for this article can be found in an online appendix at http://diabetes.diabetesjournals.org.
BAC, bacterial artificial chromosome; DHPLC, denaturing high-performance liquid chromatography; LD, linkage disequilibrium; LOD, logarithm of odds; RFLP, restriction fragment length polymorphism; SNP, single-nucleotide polymorphism; UTR, untranslated region.
- DIABETES
