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Genomic variation in pancreatic ion channel genes in Japanese type 2 diabetic patients
Author(s) -
Yamada Yuichiro,
Kuroe Akira,
Li Qing,
Someya Yoshimichi,
Kubota Akira,
Ihara Yu,
Tsuura Yoshiyuki,
Seino Yutaka
Publication year - 2001
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.193
Subject(s) - variation (astronomy) , gene , genetics , biology , physics , astrophysics
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 α 1D 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 α 1D 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 α 1D 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 α 1D 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.