The relationship between diastolic blood pressure and coronary artery calcification is dependent on single nucleotide polymorphisms on chromosome 9p21.3.

• Type of Material: Article
• Authors: Daniel S Kim, University of Michigan School of Public Health; Jennifer A Smith, University of Michigan School of Public Health; Lawrence F Bielak, University of Michigan School of Public Health; Chun-Yi Wu, University of Michigan School of Public Health; Yan Sun, Emory University; Patrick F Sheedy, Mayo Clinic; Stephen T Turner, Mayo Clinic; Patricia A Peyser, University of Michigan School of Public Health; Sharon LR Kardia, University of Michigan School of Public Health
• Language: English
• Date: 2014
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © 2014 Kim et al.; licensee BioMed Central Ltd.
• License: Creative Commons Creative Commons CC0 1.0 Universal
• Final Published Version (URL): http://dx.doi.org/10.1186/s12881-014-0089-2
• Title of Journal or Parent Work: BMC Medical Genetics
• ISSN: 1471-2350
• Volume: 15
• Start Page: 89
• End Page: 89
• Grant/Funding Information: This paper was supported by the National Institutes of Health research grants R01 HL087660, R01 HL46292, U01 HL54457, and U01 HL054481. DSK was supported in part by the Sarnoff Cardiovascular Research Fellowship for Medical Students, the Benjamin and Margaret Hall Endowed Fellowship in Genome Sciences, and NIH 5T31HG000035-18.; DSK was supported in part by the Sarnoff Cardiovascular Research Fellowship for Medical Students, Benjamin and Margaret Hall Endowed Fellowship in Genome Sciences, a Markey Foundation award, and National Institutes of Health 5T31HG000035-18 and 1F31MH101905-01.
• Keywords: RNA, Long Noncoding; Chromosomes, Human, Pair 9; Male; Genetic Variation; Aged; Genome-Wide Association Study; Middle Aged; Blood Pressure; Humans; Polymorphism, Single Nucleotide; Tomography, X-Ray Computed; Genome, Human; Female; Coronary Artery Disease; Calcinosis; Cohort Studies
• Research Categories: Health Sciences, Radiology; Health Sciences, General; Health Sciences, Epidemiology

Abstract

Single nucleotide polymorphisms (SNPs) within the 9p21.3 genomic region have been consistently associated with coronary heart disease (CHD), myocardial infarction, and quantity of coronary artery calcification (CAC), a marker of subclinical atherosclerosis. Prior studies have established an association between blood pressure measures and CAC. To examine mechanisms by which the 9p21.3 genomic region may influence CHD risk, we investigated whether SNPs in 9p21.3 modified associations between blood pressure and CAC quantity. As part of the Genetic Epidemiology Network of Arteriopathy (GENOA) Study, 974 participants underwent non-invasive computed tomography (CT) to measure CAC quantity. Linear mixed effects models were used to investigate whether seven SNPs in the 9p21.3 region modified the association between blood pressure levels and CAC quantity. Four SNPs of at least marginal significance in GENOA for a SNP-by-diastolic blood pressure (DBP) interaction were then tested for replication in the Framingham Heart Study's Offspring Cohort (N = 1,140). We found replicated evidence that one SNP, rs2069416, in CDKN2B-AS1, significantly modified the association between DBP and CAC quantity (combined P = 0.0065; Bonferroni-corrected combined P = 0.0455). Our results represent a novel finding that the relationship between DBP and CAC is dependent on genetic variation in the 9p21.3 region. Thus, variation in 9p21.3 may not only be an independent genetic risk factor for CHD, but also may modify the association between DBP levels and the extent of subclinical coronary atherosclerosis.