Studies in 3,523 Norwegians and Meta-Analysis in 11,571 Subjects Indicate That Variants in the Hepatocyte Nuclear Factor 4[alpha] (HNF4A) P2 Region Are Associated With Type 2 Diabetes in Scandinavians

Recent publications have found an association between common variants near the hepatocyte nuclear factor 4 alpha (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 inconsistenci...

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Published inDiabetes (New York, N.Y.) Vol. 56; no. 12; p. 3112
Main Authors Johansson, Stefan, Ræder, Helge, Eide, Stig Å, Midthjell, Kristian, Hveem, Kristian, Søvik, Oddmund, Molven, Anders, Njølstad, Pål Rasmus
Format Journal Article
LanguageEnglish
Published New York American Diabetes Association 01.12.2007
Subjects
Diabetes
Genotype & phenotype
Haplotypes
Insulin
Meta-analysis
Research design
Software
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Summary:Recent publications have found an association between common variants near the hepatocyte nuclear factor 4 alpha (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. 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. 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. 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.
ISSN:0012-1797
1939-327X