TCF7L2 genetic variants and progression to diabetes in the Chinese population: Pleiotropic effects on insulin secretion and insulin resistance
Journal
Journal of Molecular Medicine
Journal Volume
88
Journal Issue
2
Pages
183-192
Date Issued
2010
Author(s)
Chiu Y.-F.
Ho L.L.-T.
Ting C.-T.
Shih K.-C.
Curb J.D.
Chen Y.-D.I.
Abstract
TCF7L2 genetic variants were associated with progression to type 2 diabetes in Europeans. However, the role of TCF7L2 in type 2 diabetes remained uncertain in Chinese. Seventeen tag single nucleotide polymorphisms were genotyped in 1,094 subjects of Chinese origin from the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance family study. At baseline, the rs7903146 T allele in the exon 4 linkage disequilibrium (LD) block were associated with lower insulinogenic index at 60 min (P = 0.01), while the rs290481 G allele near the 3′ end was associated with higher 2-h post-challenge glucose (P = 0.003) and insulin concentration (P = 0.02), elevated systolic (P = 0.01) and diastolic blood pressure (P = 0.006), lower waist circumference (P = 0.01), and increased steady-state plasma glucose (SSPG) concentration measured with modified insulin suppression test (P = 0.02). Over an average follow-up period of 5.43 years, participants with the rs7903146 T allele or variants in the same LD block, but not those with the rs290481 G allele, were more likely to progress to diabetes (hazard ratio = 2.61, 95% confidence interval, 1.27-5.39, P = 0.009) than were non-carriers. TCF7L2 gene expression was inversely associated with SSPG in human visceral (r = -0.73, P = 0.006) and subcutaneous adipose tissue (r = -0.62, P = 0.03). TCF7L2 may exert pleiotropic effects on insulin secretion or insulin resistance. However, only variants associated with impaired β-cell function predict progression to diabetes in Chinese. ? 2009 Springer-Verlag.
SDGs
Other Subjects
transcription factor 7 like 2; adult; article; cell function; Chinese; controlled study; diastolic blood pressure; exon; female; gene frequency; gene linkage disequilibrium; genetic association; genetic risk; genetic variability; genotype; glucose blood level; human; hypertension; incidence; insulin release; insulin resistance; insulin sensitivity; major clinical study; male; non insulin dependent diabetes mellitus; pancreas islet beta cell; population genetics; single nucleotide polymorphism; systolic blood pressure; Adult; Asian Continental Ancestry Group; Cohort Studies; Diabetes Mellitus, Type 2; Disease Progression; Family; Female; Genetic Variation; Humans; Incidence; Insulin; Insulin Resistance; Male; Middle Aged; Polymorphism, Single Nucleotide; TCF Transcription Factors
Type
journal article