The haplotypes of the IRS-2 gene affect insulin sensitivity in Japanese patients with type 2 diabetes.
A commonly occurring nucleotide polymorphism of the insulin-receptor substrate 2 (IRS-2) gene at amino acid 1057 from Glycine to Asparaginic acid (G1057D) was recently shown to be a determinant of insulin sensitivity in both glucose-tolerant individuals and those with type 2 diabetes. With respect to the latter, the IRS-2 D1057 allele increase the risk of insulin resistance among obese individuals. After we reconstructed haplotypes from the G1057D variant and the -769C/T replacement that was newly identified, we investigated the possibility that the IRS-2 gene affects insulin sensitivity in Japanese glucose-tolerant subjects (n = 260) and type 2 diabetic patients (n = 123). We did not find that the D1057 allele and haplotype pairs were associated with the risk of diabetes. However, type 2 diabetic patients, particularly obese patients, carrying the D1057 allele and the CA haplotype were associated with insulin resistance. Furthermore, we suggested that the TG and CG haplotypes might have a protective role against insulin resistance. This observation raises the possibility that both the IRS-2 D1057 allele and the CA haplotype are useful genetic markers for identifying obese individuals who are particularly susceptible to insulin resistance.
Okazawa
Kayoko
K
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Yoshimasa
Yasunao
Y
Miyamoto
Yoshihiro
Y
Takahashi-Yasuno
Akiko
A
Miyawaki
Takashi
T
Masuzaki
Hiroaki
H
Hayashi
Tatsuya
T
Hosoda
Kiminori
K
Inoue
Gen
G
Nakao
Kazuwa
K
D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D005808:Genes, Recessive; D006239:Haplotypes; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins; D007564:Japan; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins