Studies in 3,523 Norwegians (HUNT2) and Meta-Analysis in 11,571 Subjects Indicate that Variants in the HNF4A P2 Region are Associated with Type 2 Diabetes in Scandinavians
- Stefan Johansson1,,2,
- Helge Ræder1,,3,
- Stig Å Eide1,,2,
- Kristian Midthjell4,
- Kristian Hveem4,
- Oddmund Søvik1,
- Anders Molven5,,6 and
- Pål Rasmus Njølstad (pal.njolstad{at}uib.no)1,,3
- From the 1Department of Clinical Medicine, University of Bergen, Bergen, Norway
- the 2Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway
- the 3Department of Pediatrics, Haukeland University Hospital, Bergen, Norway
- the 4HUNT Research Center, Department of Public Health and General Practice, Norwegian University of Science and Technology, Verdal, Norway
- the 5Gade Institute, University of Bergen, Norway; and
- the 6Department of Pathology, Haukeland University Hospital, Bergen, Norway
Abstract
OBJECTIVE: Recent publications have found an association between common variants near the 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 SNPs in a large population-based sample and included a meta-analysis of published studies.
RESEARCH DESIGN AND METHODS: We genotyped twelve SNPs in the HNF4A region in a Norwegian population-based sample of 1,644 individuals with type 2 diabetes and 1,879 controls (The HUNT2 Study). 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 towards association for the SNPs rs1884613 (OR = 1.17 <1.03-1.35>) and rs2144908 (OR = 1.21 <1.05-1.38>) in the P2 region and for rs4812831 (OR = 1.21 <1.02-1.44>) located 34 kb downstream of the P2 promoter. Meta-analysis, comprising 12,292 type 2 diabetes cases and 15,519 controls, revealed a non-significant OR of 1.05 <0.98-1.12> but with significant heterogeneity between the populations. We therefore performed a sub-analysis including only the data for subjects from Scandinavia. Among the 4,000 Scandinavian cases and 7,571 controls, 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.
Footnotes
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- Received April 12, 2007.
- Accepted September 4, 2007.
- Copyright © American Diabetes Association
