title: TCF7L2 genetic variants and progression to diabetes in the Chinese population: pleiotropic effects on insulin secretion and insulin resistance.
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 beta-cell function predict progression to diabetes in Chinese.
authors.affiliation: Internal Medicine, National Taiwan University Hospital Yunlin Branch, Douliou, Yunlin, Taiwan.
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Chang
authors.forename: Yen-Feng
authors.initials: YF
authors.lastname: Chiu
authors.forename: Larry Low-Tone
authors.initials: LL
authors.lastname: Ho
authors.forename: Chih-Tai
authors.initials: CT
authors.lastname: Ting
authors.forename: Kuang-Chung
authors.initials: KC
authors.lastname: Shih
authors.forename: J David
authors.initials: JD
authors.lastname: Curb
authors.forename: Yii-Der Ida
authors.initials: YD
authors.lastname: Chen
authors.forename: Hung-Yuan
authors.initials: HY
authors.lastname: Li
authors.forename: Lee-Ming
authors.initials: LM
authors.lastname: Chuang
mesh_terms: D000328:Adult; D044466:Asian People; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics* / Q000503:physiopathology; D018450:Disease Progression; D005190:Family; D005260:Female; D014644:Genetic Variation; D006801:Humans; D015994:Incidence; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051820:TCF Transcription Factors / Q000235:genetics* / Q000378:metabolism; D058118:Transcription Factor 7-Like 2 Protein
chemical_list: D007328:Insulin; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein