A population association study of four candidate genes (hexokinase II, glucagon-like peptide-1 receptor, fatty acid binding protein-2, and apolipoprotein C-II) with type 2 diabetes and impaired glucose tolerance in Japanese subjects.

In order to define the major genetic factor(s) for the development of Type 2 (non-insulin-dependent) diabetes mellitus in Japanese subjects, a population association study of candidate genes involved in either glucose or lipid metabolism was carried out using microsatellite DNA polymorphisms. Each polymorphic locus near the four candidate genes, hexokinase II (HKII), glucagon-like peptide-1 receptor (GLP1R), fatty acid binding protein-2 (FABP-2), and apolipoprotein C-II (apoC-II) genes, were amplified by polymerase chain reaction (PCR) using 32P-labelled primers and each subject was genotyped for the association study. The HKII, GLP1R, FABP-2, and apoC-II polymorphisms exhibited 18, 10, 7, and 10 alleles, respectively. While polymorphism information contents (PICs) of these polymorphisms were relatively high, allele frequencies in these polymorphisms did not differ among subjects with Type 2 diabetes, impaired glucose tolerance (IGT) and non-diabetic controls. These results suggest that the HKII, GLP1R, FABP-2, and apoC-II genes are not the major inherited factors for the development of Type 2 diabetes or IGT in Japanese subjects, although minor contribution cannot be ruled out.