New amino acid substitutions in the IRS-2 gene in Finnish and Chinese subjects with late-onset type 2 diabetes

We investigated the significance of the variants of the IRS-2 gene in patie nts with type 2 diabetes. The entire coding part of the IRS-2 gene was scre ened by single-strand conformation polymorphism analysis in 40 Chinese and 40 Finnish patients with late-onset type 2 diabetes. The association of the variants of the IRS-2 gene with type 2 diabetes was studied in 85 Finnish diabetic patients and 82 Finnish control subjects and in 100 Chinese diabet ic patients and 85 Chinese control subjects. The four variants predicting s tructural changes in the insulin receptor substrate (IRS)-2 protein include d an insertion of AAC (Asn) in the Asn repeat sequence centered around codo ns 29-36 (allele frequencies of 0 vs. 0.6% and 1.5 vs. 0%), the Ala157Thr s ubstitution (0 vs. 0% and 0.5 vs. 0%), the Leu647Val substitution (0.6 vs. 0% and 0 vs. 0%), and the Gly1057Asp polymorphism (31 vs. 31% and 35 vs. 30 %) (P = NS for all comparisons). Furthermore, six silent variants were obse rved (CGC147CGG, CCC155CCG, GCC156GCT, AGT723AGC, TGT816TGC, and CCC829CCT) . The Gly1057Asp polymorphism was not associated with insulin resistance or impaired insulin secretion in Finnish subjects with normal glucose toleran ce (n = 295) or impaired glucose tolerance (n = 38). These data indicate th at structural variants of the IRS-2 gene were uncommon in Finnish and Chine se patients with type 2 diabetes. Thus, the variants in the coding part of the IRS-2 gene are unlikely to have a major role in the development of type 2 diabetes in Finnish or Chinese subjects.