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 Rasmus; Johansson, Stefan
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.