PT  - JOURNAL ARTICLE
AU  - Johansson, Stefan
AU  - Ræder, Helge
AU  - Eide, Stig Å
AU  - Midthjell, Kristian
AU  - Hveem, Kristian
AU  - Søvik, Oddmund
AU  - Molven, Anders
AU  - Njølstad, Pål Rasmus
TI  - Studies in 3,523 Norwegians and Meta-Analysis in 11,571 Subjects Indicate That Variants in the Hepatocyte Nuclear Factor 4α (HNF4A) P2 Region Are Associated With Type 2 Diabetes in Scandinavians
AID  - 10.2337/db07-0513
DP  - 2007 Dec 01
TA  - Diabetes
PG  - 3112--3117
VI  - 56
IP  - 12
4099  - http://diabetes.diabetesjournals.org/content/56/12/3112.short
4100  - http://diabetes.diabetesjournals.org/content/56/12/3112.full
SO  - Diabetes2007 Dec 01; 56
AB  - OBJECTIVE— Recent publications have found an association between common variants near the hepatocyte nuclear factor 4α (HNF4A) P2 promoter and type 2 diabetes in some populations but not in others, and the role for HNF4A in type 2 diabetes has remained unclear. In an attempt to address these inconsistencies, we investigated HNF4A single nucleotide polymorphisms (SNPs) in a large population-based sample and included a meta-analysis of published studies.RESEARCH DESIGN AND METHODS— We genotyped 12 SNPs in the HNF4A region in a Norwegian population–based sample of 1,644 individuals with type 2 diabetes and 1,879 control subjects (the Nord-Trøndelag Health Study [HUNT] 2). We combined our data with all previously published case/control studies and performed a meta-analysis.RESULTS— Consistent with initial studies, we found a trend toward association for the SNPs rs1884613 (odds ratio [OR] 1.17 [95% CI 1.03–1.35]) and rs2144908 (1.21 [1.05–1.38]) in the P2 region and for rs4812831 (1.21 [1.02–1.44]), located 34 kb downstream of the P2 promoter. Meta-analysis, comprising 12,292 type 2 diabetic case and 15,519 control subjects, revealed a nonsignificant OR of 1.05 (95% CI 0.98–1.12) but with significant heterogeneity between the populations. We therefore performed a subanalysis including only the data for subjects from Scandinavia. Among the 4,000 case and 7,571 control Scandinavian subjects, a pooled OR of 1.14 (1.06–1.23), P = 0.0004, was found for the SNP rs1884613.CONCLUSIONS— Our results suggest that variation in the HNF4A region is associated with type 2 diabetes in Scandinavians, highlighting the importance of exploring small genetic effects in large, homogenous populations.