A variant in CDKAL1 influences insulin response and risk of type 2 diabetes.
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Walters, G Bragi
Ng, Maggie C Y
Wilensky, Robert L
Reilly, Muredach P
Ma, Ronald C Y
van Vliet-Ostaptchouk, Jana V
Hofker, Marten H
Rader, Daniel J
Chan, Juliana C N
Gulcher, Jeffrey R
MetadataShow full item record
CitationNat. Genet. 2007, 39(6):770-5
AbstractWe 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.
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