The Chromosome 9p21 CVD- and T2D-Associated Regions in a Norwegian Population (The HUNT2 Survey)
Helgeland, Øyvind; Hertel, Jens Kristoffer; Molven, Anders; Ræder, Helge; Platou, Carl Geoffrey Parrinder; Midthjell, Kristian; Hveem, Kristian; Nygård, Ottar; Njølstad, Pål R.; Johansson, Stefan
Peer reviewed, Journal article
Published version
Åpne
Permanent lenke
https://hdl.handle.net/1956/10183Utgivelsesdato
2015Metadata
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Originalversjon
https://doi.org/10.1155/2015/164652Sammendrag
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.