A variant in CDKAL1 influences insulin response and risk of type 2 diabetes.
Steinthorsdottir V,
Thorleifsson G,
Reynisdottir I,
Benediktsson R,
Jonsdottir T,
Walters GB,
Styrkarsdottir U,
Gretarsdottir S,
Emilsson V,
Ghosh S,
Baker A,
Snorradottir S,
Bjarnason H,
Ng MC,
Hansen T,
Bagger Y,
Wilensky RL,
Reilly MP,
Adeyemo A,
Chen Y,
Zhou J,
Gudnason V,
Chen G,
Huang H,
Lashley K,
Doumatey A,
So WY,
Ma RC,
Andersen G,
Borch-Johnsen K,
Jorgensen T,
van Vliet-Ostaptchouk JV,
Hofker MH,
Wijmenga C,
Christiansen C,
Rader DJ,
Rotimi C,
Gurney M,
Chan JC,
Pedersen O,
Sigurdsson G,
Gulcher JR,
Thorsteinsdottir U,
Kong A,
Stefansson K.
deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland. vstein@decode.is
We conducted a genome-wide association study for type 2 diabetes (T2D) in Icelandic cases and controls, and we found that a previously described variant in the transcription factor 7-like 2 gene (TCF7L2) gene conferred the most significant risk. In addition to confirming two recently identified risk variants, we identified a variant in the CDKAL1 gene that was associated with T2D in individuals of European ancestry (allele-specific odds ratio (OR) = 1.20 (95% confidence interval, 1.13-1.27), P = 7.7 x 10(-9)) and individuals from Hong Kong of Han Chinese ancestry (OR = 1.25 (1.11-1.40), P = 0.00018). The genotype OR of this variant suggested that the effect was substantially stronger in homozygous carriers than in heterozygous carriers. The ORs for homozygotes were 1.50 (1.31-1.72) and 1.55 (1.23-1.95) in the European and Hong Kong groups, respectively. The insulin response for homozygotes was approximately 20% lower than for heterozygotes or noncarriers, suggesting that this variant confers risk of T2D through reduced insulin secretion.
PMID: 17460697 [PubMed - indexed for MEDLINE]