title: The relationship between diastolic blood pressure and coronary artery calcification is dependent on single nucleotide polymorphisms on chromosome 9p21.3.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Kim
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Smith
authors.forename: Lawrence F
authors.initials: LF
authors.lastname: Bielak
authors.forename: Chun-Yi
authors.initials: CY
authors.lastname: Wu
authors.forename: Yan V
authors.initials: YV
authors.lastname: Sun
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Sheedy
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Turner
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Peyser
authors.affiliation: Department of Epidemiology, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor 48109, MI, USA. skardia@umich.edu.
authors.forename: Sharon L R
authors.initials: SL
authors.lastname: Kardia
mesh_terms: D000368:Aged; D001794:Blood Pressure / Q000235:genetics*; D002114:Calcinosis / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D062085:RNA, Long Noncoding / Q000235:genetics*; D014057:Tomography, X-Ray Computed
chemical_list: C561518:CDKN2B antisense RNA, human; D062085:RNA, Long Noncoding