Variants of the transcription factor 7-like 2 (TCF7L2) gene are associated with type 2 diabetes in an African-American population enriched for nephropathy.
OBJECTIVE
Recently, variants in the TCF7L2 gene have been reported to be associated with type 2 diabetes across multiple Europid populations, but only one small sample of African-American type 2 diabetic patients has been examined. Our objective was to investigate the importance of TCF7L2 in a larger African-American case-control population.


METHODS
We investigated single nucleotide polymorphisms (SNPs) in six known type 2 diabetes genes in 577 African-American case subjects with type 2 diabetes enriched for nephropathy and 596 African-American control subjects. Additionally, we genotyped 70 ancestry-informative markers (AIMs) to apply adjustments for differences in ancestral proportions.


RESULTS
The most significant associations were observed with TCF7L2 intron 3 SNPs rs7903146 (additive P = 4.10 x 10(-6), odds ratio [OR] 1.51; admixture-adjusted P(a) = 3.77 x 10(-6)) and rs7901695 (P = 0.001, OR 1.30; P(a) = 0.003). The 2-SNP haplotype containing these SNPs was also associated with type 2 diabetes (P = 3 x 10(-5)). Modest associations were also seen with TCF7L2 intron 4 SNPs rs7895340, rs11196205, and rs12255372 (0.01 < P < 0.05; 0.03 < P(a) < 0.08), as well as with ATP-sensitive inwardly rectifying potassium channel subunit Kir6.2 (KCNJ11) and hepatocyte nuclear factor 4-alpha (HNF4A) SNPs (0.01 < P < 0.05; 0.01 < P(a) < 0.41). No significant associations were detected with genotyped calpain 10 (CAPN10), peroxisome proliferator-activated receptor gamma (PPARG), and transcription factor 1 (TCF1) SNPs.


CONCLUSIONS
This study indicates that variants in the TCF7L2 gene significantly contribute to diabetes susceptibility in African-American populations.
Sale
Michèle M
MM
Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA. msale@virginia.edu
Smith
Shelly G
SG
Mychaleckyj
Josyf C
JC
Keene
Keith L
KL
Langefeld
Carl D
CD
Leak
Tennille S
TS
Hicks
Pamela J
PJ
Bowden
Donald W
DW
Rich
Stephen S
SS
Freedman
Barry I
BI
D001741:Black or African American / Q000235:genetics*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D051820:TCF Transcription Factors / Q000235:genetics*; D058118:Transcription Factor 7-Like 2 Protein; D014481:United States
D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein