A genetic risk variant for myocardial infarction on chromosome 6p24 is associated with impaired central hemodynamic indexes

Riyaz S. Patel, Alanna A. Morris, Yusuf Ahmed, Nino Kavtaradze, Salman Sher, Shaoyong Su, A. Maziar Zafari, Rebecca Din-Dzietham, Salina P. Waddy, Viola Vaccarino, R. Wayne Alexander, Gary Gibbons, Arshed A. Quyyumi

Research output: Contribution to journalArticle

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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.MethodsSingle- 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).ResultsOf 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%.ConclusionsThe 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.

Original languageEnglish (US)
Pages (from-to)797-803
Number of pages7
JournalAmerican journal of hypertension
Volume25
Issue number7
DOIs
StatePublished - Jul 1 2012

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Chromosomes
Hemodynamics
Myocardial Infarction
Pulse Wave Analysis
Genome-Wide Association Study
Pressure
Single Nucleotide Polymorphism
Population
Blood Pressure
Protein Phosphatase 1
Regulator Genes
Arterial Pressure
Body Mass Index
Cardiovascular Diseases
Nucleotides
Smoking
Alleles
Cholesterol
Phenotype
Glucose

Keywords

  • 6p24
  • GWAS
  • SNP
  • augmentation index
  • blood pressure
  • elasticity
  • genetic
  • genomic
  • hypertension
  • myocardial infarction
  • stiffness

ASJC Scopus subject areas

  • Internal Medicine

Cite this

A genetic risk variant for myocardial infarction on chromosome 6p24 is associated with impaired central hemodynamic indexes. / Patel, Riyaz S.; Morris, Alanna A.; Ahmed, Yusuf; Kavtaradze, Nino; Sher, Salman; Su, Shaoyong; Zafari, A. Maziar; Din-Dzietham, Rebecca; Waddy, Salina P.; Vaccarino, Viola; Alexander, R. Wayne; Gibbons, Gary; Quyyumi, Arshed A.

In: American journal of hypertension, Vol. 25, No. 7, 01.07.2012, p. 797-803.

Research output: Contribution to journalArticle

Patel, RS, Morris, AA, Ahmed, Y, Kavtaradze, N, Sher, S, Su, S, Zafari, AM, Din-Dzietham, R, Waddy, SP, Vaccarino, V, Alexander, RW, Gibbons, G & Quyyumi, AA 2012, 'A genetic risk variant for myocardial infarction on chromosome 6p24 is associated with impaired central hemodynamic indexes', American journal of hypertension, vol. 25, no. 7, pp. 797-803. https://doi.org/10.1038/ajh.2012.41
Patel, Riyaz S. ; Morris, Alanna A. ; Ahmed, Yusuf ; Kavtaradze, Nino ; Sher, Salman ; Su, Shaoyong ; Zafari, A. Maziar ; Din-Dzietham, Rebecca ; Waddy, Salina P. ; Vaccarino, Viola ; Alexander, R. Wayne ; Gibbons, Gary ; Quyyumi, Arshed A. / A genetic risk variant for myocardial infarction on chromosome 6p24 is associated with impaired central hemodynamic indexes. In: American journal of hypertension. 2012 ; Vol. 25, No. 7. pp. 797-803.
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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.MethodsSingle- 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).ResultsOf 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{\%}.ConclusionsThe 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.",
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author = "Patel, {Riyaz S.} and Morris, {Alanna A.} and Yusuf Ahmed and Nino Kavtaradze and Salman Sher and Shaoyong Su and Zafari, {A. Maziar} and Rebecca Din-Dzietham and Waddy, {Salina P.} and Viola Vaccarino and Alexander, {R. Wayne} and Gary Gibbons and Quyyumi, {Arshed A.}",
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T1 - A genetic risk variant for myocardial infarction on chromosome 6p24 is associated with impaired central hemodynamic indexes

AU - Patel, Riyaz S.

AU - Morris, Alanna A.

AU - Ahmed, Yusuf

AU - Kavtaradze, Nino

AU - Sher, Salman

AU - Su, Shaoyong

AU - Zafari, A. Maziar

AU - Din-Dzietham, Rebecca

AU - Waddy, Salina P.

AU - Vaccarino, Viola

AU - Alexander, R. Wayne

AU - Gibbons, Gary

AU - Quyyumi, Arshed A.

PY - 2012/7/1

Y1 - 2012/7/1

N2 - 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.MethodsSingle- 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).ResultsOf 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%.ConclusionsThe 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.

AB - 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.MethodsSingle- 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).ResultsOf 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%.ConclusionsThe 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.

KW - 6p24

KW - GWAS

KW - SNP

KW - augmentation index

KW - blood pressure

KW - elasticity

KW - genetic

KW - genomic

KW - hypertension

KW - myocardial infarction

KW - stiffness

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