Variant of transcription factor 7-like 2 (TCF7L2) gene and the risk of type 2 diabetes in large cohorts of U.S. women and men.
Emerging evidence indicates that variation in the transcription factor 7-like 2 (TCF7L2) gene may play a role in the pathogenesis of type 2 diabetes. In a prospective, nested, case-control study (n = 3,520) within the Nurses' Health Study (687 type 2 diabetic case and 1,051 control subjects) and the Health Professionals Follow-up Study (886 case and 896 control subjects), we examined the association of a common variant of the TCF7L2 gene (rs12255372 [T/G]) with type 2 diabetes risk among Caucasians. Frequencies of the T-allele were significantly higher among case than control subjects; each copy of the T-allele was associated with a 1.32-fold (P = 0.0002) and 1.53-fold (P < 0.0001) increased type 2 diabetes risk in women and men, respectively. The odds ratios (95% CI) associated with homozygous carriers of the T-allele were 1.86 (1.30-2.67) and 2.15 (1.48-3.13) in women and men, respectively. Population-attributable risks for diabetes associated with the T-allele were 14.8 and 22.3% for women and men, respectively. In a meta-analysis of 3,347 case and 3,947 control subjects, each copy of the T-allele was associated with a 1.48-fold increased risk (P < 10(-16)). Our findings confirm that the TCF7L2 gene represents an important locus for predicting inherited susceptibility to type 2 diabetes.
Zhang
Cuilin
C
Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA. cuilin.zhang@channing.harvard.edu
Qi
Lu
L
Hunter
David J
DJ
Meigs
James B
JB
Manson
JoAnn E
JE
van Dam
Rob M
RM
Hu
Frank B
FB
D000328:Adult; D000368:Aged; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors; D051820:TCF Transcription Factors / Q000235:genetics*; D058118:Transcription Factor 7-Like 2 Protein; D014481:United States; D044465:White People / Q000235:genetics
D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein