Sequence variations of the pancreatic islet/liver glucose transporter (GLUT2) gene in Japanese subjects with noninsulin dependent diabetes mellitus
- Yamaguchi Univ. School of Medicine (Japan); and others
To assess the genetic susceptibility to noninsulin-dependent diabetes mellitus (NIDDM) in Japanese subjects, we investigated the role of GLUT2 gene defects in patients with NIDDM. When the allelic frequency of a simple tandem repeat polymorphism in the GLUT2 gene was compared, the allele with 155 base pairs was more common in NIDDM patients (n = 99) than in controls (n = 89; 5.1% v. 0.6%; P = 0.0118, by Fisher`s exact test), whereas this was not significant after the correction for multiple comparisons. To directly identify mutations, we then analyzed each of 11 exons by the polymerase chain reaction-single strand conformation polymorphism analysis in 60 NIDDM patients. We found 2 missense mutations in exon 3: CCC{r_arrow}CTC (Pro{sup 68}{r_arrow}Leu) in 1 patient and ACT{r_arrow}ATT (Thr{sup 110}{r_arrow}Ile) in 3 patients, all in the heterozygous state. These mutations were found in 60 control subjects. To evaluate the significance of the Pro{sup 68}{r_arrow}Leu mutation, the family members of the proband were studied. The mutation did not appear to be associated with the disease or other clinical parameters including change in immunoreactive insulin/change in plasma glucose or oral glucose load. The other mutation (Thr{sup 110}{r_arrow}Ile) is known to be functionally insignificant. We identified 4 additional nucleotide changes, all of which appeared to be silent. We concluded that the mutations in the GLUT2 gene were not major determinants of genetic susceptibility to NIDDM in Japanese. 34 refs., 2 figs., 3 tabs.
- OSTI ID:
- 443616
- Journal Information:
- Journal of Clinical Endocrinology and Metabolism, Vol. 80, Issue 10; Other Information: PBD: Oct 1995
- Country of Publication:
- United States
- Language:
- English
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