Identification of two novel amino acid polymorphisms in beta-cell/liver (GLUT2) glucose transporter in Japanese subjects

Abstract

SummaryThe beta-cell/liver glucose transporter (GLUT2) gene was screened for mutations using single-strand conformation polymorphism analysis (SSCP) in 30 Japanese subjects with non-insulin dependent diabetes mellitus (NIDDM). Analysis of all exons and adjacent intron regions identified six SSCP polymorphisms, three of which resulted in amino acid substitutions: V101I, Tll0I and G519E. The V101I and G519E substitutions represent new polymorphisms in this gene. The six polymorphisms were observed in both NIDDM and control groups and there were no significant differences in allele frequencies between groups. A portion of the insulin receptor substrate i gene in 30 NIDDM subjects and in normal control subjects was also screened for mutations. Two SSCP variants that change the sequence of the protein, AS686/687 (deletion of the codons for serine-686 and 687) and G972R, were identified in two different NIDDM subjects, both whom were also heterozygous for the V101I polymorphism in GLUT2. The GLUT2 and IRS1 amino acid polymorphisms did not show a simple pattern of co-inheritance with NIDDM in the families of these subjects suggesting that neither polymorphism is sufficient to cause NIDDM but may increase diabetes-susceptibility through their interaction with other loci and environmental factors. [Diabetologia (1995) 38: 211-215]

Physical activity modifies the effect of SNPs in theSLC2A2(GLUT2) andABCC8(SUR1) genes on the risk of developing type 2 diabetes

“…Recently, the association of the T110I polymorphism in SLC2A2 with the risk of type 2 diabetes among Finnish subjects was replicated (50). The results of other case control studies with respect to SNPs in SLC2A2 and ABCC8 and risk of type 2 diabetes have, however, been inconsistent (1,2,13,15,32,34,36,39,40,43,47), whereas a meta-analysis confirmed the association of the K allele of the E23K polymorphism in KCNJ11with an increased risk of type 2 diabetes among Caucasians (47). The prospective DPP, however, unexpectedly found a lower risk of conversion from IGT to type 2 diabetes in the carriers of the K allele (14).…”

A missense mutation in the CD38 gene, a novel factor for insulin secretion: association with Type II diabetes mellitus in Japanese subjects and evidence of abnormal function when expressed in vitro

“…Thus, this mutation is associated with Japanese Type II diabetes mellitus having a familial aggregation of this disease. Indeed, one patient with this mutation has the Val 101 Ile and Gly 519 Glu mutations on the beta cell/liver glucose transporter (GLUT2) gene, and her mother, with impaired glucose tolerance, has this mutation on the CD38 gene and the Val 101 Ile mutation on the GLUT2 gene [28]. In these patients, the decreased function of CD38 mutant may contribute to the impairment of the glucose-stimulated insulin secretion in association with the GLUT2 mutants.…”

High frequency of polymorphism but no mutations found in the GLUT1 glucose transporter gene in NIDDM and familial obesity by SSCP analysis

“…One NIDDM and one obese patient had three concomitant nucleotide substitutions in exons 2, 5 and 9. It should be pointed out that the same amount of sequence polymorphism has been shown for both the GLUT2 and GLUT4 genes in NIDDM and controls (Bjorbaek et al 1994;Shimada et al 1995). Despite this high level of polymorphism, none of the nucleotide changes determined significant mutation.…”