title: A genetic risk variant for myocardial infarction on chromosome 6p24 is associated with impaired central hemodynamic indexes.
abstract: BACKGROUND
  Genome-wide association studies (GWAS) have identified novel variants associated with myocardial infarction (MI) in Caucasians. We hypothesized that those variants whose mechanism of risk is currently unknown, confer risk via pathways mediating arterial wave reflections which is an increasingly recognized risk factor for cardiovascular disease.
  
  
  METHODS
  Single-nucleotide polymorphisms (SNPs) at eight MI risk loci were genotyped and correlated with noninvasively determined pulse wave analysis (PWA)-derived central hemodynamic indexes (augmentation index (AIx); augmented pressure (AP); time to reflected wave (TrW) and central systolic blood pressure (SBP) and diastolic BP (DBP)) in two independent Caucasian populations including (i) those free of measured cardiovascular risk factors (n = 133) and (ii) a community-based population (n = 270).
  
  
  RESULTS
  Of the eight SNPs examined in the healthy group, the variants at loci 6p24 (AIx and AP both P < 0.001, TrW P = 0.02) and 21q22 (AIx P = 0.002, TrW P = 0.037) were significantly associated with PWA indexes. In the replication group, only the 6p24 variant correlated with these phenotypes (AIx P = 0.005, AP P = 0.049, TrW P = 0.013). In the pooled population (n = 403), no new associations were identified but the association with 6p24 and AIx remained significant even after Bonferroni correction and adjustment for covariates including age, mean arterial pressure, height, gender, glucose, cholesterol, body mass index (BMI), and smoking (AIx (P = 0.03)). Each copy of the risk allele C increased the AIx by 3.5%.
  
  
  CONCLUSIONS
  The GWAS discovered MI risk variant at 6p24 in the protein phosphatase 1 regulator gene (PHACTR1) is associated with adverse arterial wave reflection indexes and may mediate MI risk through this pathway.
authors.affiliation: Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Riyaz S
authors.initials: RS
authors.lastname: Patel
authors.forename: Alanna A
authors.initials: AA
authors.lastname: Morris
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Ahmed
authors.forename: Nino
authors.initials: N
authors.lastname: Kavtaradze
authors.forename: Salman
authors.initials: S
authors.lastname: Sher
authors.forename: Shaoyong
authors.initials: S
authors.lastname: Su
authors.forename: A Maziar
authors.initials: AM
authors.lastname: Zafari
authors.forename: Rebecca
authors.initials: R
authors.lastname: Din-Dzietham
authors.forename: Salina P
authors.initials: SP
authors.lastname: Waddy
authors.forename: Viola
authors.initials: V
authors.lastname: Vaccarino
authors.forename: R Wayne
authors.initials: RW
authors.lastname: Alexander
authors.forename: Gary
authors.initials: G
authors.lastname: Gibbons
authors.forename: Arshed A
authors.initials: AA
authors.lastname: Quyyumi
mesh_terms: D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000502:physiology; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D003935:Diagnostic Techniques, Cardiovascular; D005260:Female; D055106:Genome-Wide Association Study; D006439:Hemodynamics / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D044465:White People / Q000235:genetics
chemical_list: D008840:Microfilament Proteins; C570134:PHACTR1 protein, human