Genomic variation in pancreatic ion channel genes in Japanese type 2 diabetic patients.

Background Many genetic diseases are caused by mutations in ion channel genes. Because type 2 diabetes is characterized by pancreatic β-cell insensitivity to glucose, the genes responsible for glucose metabolism and calcium signaling in pancreatic β-cells are candidate type 2 diabetes susceptibility genes. Methods We have examined genomic variations in two ion channel genes relevant to the molecular pathology of diabetes mellitus, the Kir6.2 subunit of the ATP-sensitive potassium channel gene and α1D subunit of the voltage-dependent calcium channel (VDCC) gene among Japanese type 2 diabetic patients. Results There are two alleles in the Kir6.2 gene: EI, glutamic acid at codon 23 and isoleucine at codon 337 and KV, lysine at codon 23 and valine at codon 337. The allelic frequencies of these polymorphisms are similar in type 2 diabetic patients and normal subjects. We also detected trinucleotide repeat polymorphisms in the amino terminus and the carboxyl terminal region of the α1D gene. Expansion of the ATG trinucleotide repeat from seven to eight was detected only in type 2 diabetic patients, but the frequency was low and was similar in type 2 diabetic patients and normal subjects. Conclusions Although variations of the Kir6.2 and α1D genes are not associated with the development of common type 2 diabetes, further studies may determine the role of these genomic variations, especially those in the α1D VDCC gene, in the pathogenesis of certain subsets of type 2 diabetes, or as a co-factor in the polygenic disorder generally. Copyright © 2001 John Wiley & Sons, Ltd.