Analysis of linkage disequilibrium between polymorphisms in the KCNJ9 genewith type 2 diabetes mellitus in Pima Indians

The KCNJ9 gene encodes a G-protein-coupled inwardly rectifying potassium ch annel and is located within a region on human chromosome 1 that has been li nked with type 2 diabetes mellitus in Pima Indians and Caucasians. To asses s the potential contribution of genetic alterations within KCNJ9 to diabete s susceptibility in the Pimas, we have genotyped 11 single nucleotide polym orphisms (SNPs) in 50 Pimas with diabetes and 50 Pimas over the age of 45 w ithout diabetes and in 51 sib pairs, discordant for the disease, who were c haracterized by decreased allele sharing at the chromosomal location of the maximum LOD score, We detected three SNP clusters exhibiting distinct link age disequilibria, Polymorphisms in intron 2, exon 3, and the 3'-UTR were i n statistically significant linkage disequilibrium with diabetes in the cas e-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 compri sing 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 d etected following adjustment for one of the most strongly associated SNPs i n the entire original linkage set. Our results indicate that variants in KC NJ9 are associated with diabetes in Pimas but do not account for the linkag e of 1q with diabetes in this population. (C) 2001 Academic Press.