The Chromosome 9p21 CVD- and T2D-Associated Regions in a Norwegian Population (The HUNT2 Survey)

Øyvind Helgeland; Jens K Hertel; Anders Molven; Helge Ræder; Carl G P Platou; Kristian Midthjell; Kristian Hveem; Ottar Nygård; Pål R Njølstad; Stefan Johansson

doi:10.1155/2015/164652

The Chromosome 9p21 CVD- and T2D-Associated Regions in a Norwegian Population (The HUNT2 Survey)

Int J Endocrinol. 2015:2015:164652. doi: 10.1155/2015/164652. Epub 2015 May 18.

Authors

Affiliations

¹ KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway ; Department of Pediatrics, Haukeland University Hospital, 5021 Bergen, Norway.
² KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway ; Department of Pediatrics, Haukeland University Hospital, 5021 Bergen, Norway ; Morbid Obesity Center, Vestfold Hospital Trust, 3116 Tønsberg, Norway ; Department of Heart Disease, Haukeland University Hospital, 5021 Bergen, Norway.
³ KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway ; Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway ; Department of Pathology, Haukeland University Hospital, 5021 Bergen, Norway.
⁴ HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, 7600 Levanger, Norway ; Department of Internal Medicine, Levanger Hospital, Nord-Trøndelag Health Trust, 7600 Levanger, Norway.
⁵ HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, 7600 Levanger, Norway.
⁶ KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway ; Department of Heart Disease, Haukeland University Hospital, 5021 Bergen, Norway.
⁷ KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway ; Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, 5021 Bergen, Norway.

Abstract

Background. Two adjacent regions upstream CDKN2B on chromosome 9p21 have been associated with type 2 diabetes (T2D) and progression of cardiovascular disease (CVD). The precise location and number of risk variants have not been completely delineated and a possible synergistic relationship between the adjacent regions is not fully addressed. By a population based cross-sectional case-control design, we genotyped 18 SNPs upstream of CDKN2B tagging 138 kb in and around two LD-blocks associated with CVD and T2D and investigated associations with T2D, angina pectoris (AP), myocardial infarction (MI), coronary heart disease (CHD; AP or AMI), and stroke using 5,564 subjects from HUNT2. Results. Single point and haplotype analysis showed evidence for only one common T2D risk haplotype (rs10757282∣rs10811661: OR = 1.19, P = 2.0 × 10(-3)) in the region. We confirmed the strong association between SNPs in the 60 kb CVD region with AP, MI, and CHD (P < 0.01). Conditioning on the lead SNPs in the region, we observed two suggestive independent single SNP association signals for MI, rs2065501 (P = 0.03) and rs3217986 (P = 0.04). Conclusions. We confirmed the association of known variants within the 9p21 interval with T2D and CHD. Our results further suggest that additional CHD susceptibility variants exist in this region.