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A genome-wide association study of carotid atherosclerosis in HIV-infected men

Sadeep Shrestha1, Marguerite R Irvin, Kent D Taylor

  • 1Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, 1665 University Blvd., Birmingham, AL 35294-0022, USA. sshresth@uab.edu

AIDS (London, England)
|December 17, 2009
PubMed

Insights

Host genetics influence atherosclerosis in HIV patients on HAART. A specific gene variant (RYR3) is linked to common carotid intima-media thickness, a marker for cardiovascular disease.

Area of Science:

  • Genetics and Cardiovascular Health
  • HIV/AIDS Research
  • Medical Diagnostics

Background:

  • The genetic factors influencing subclinical atherosclerosis in individuals with HIV receiving highly active antiretroviral therapy (HAART) remain largely uncharacterized.
  • Understanding these genetic influences is crucial for managing cardiovascular risk in this population.

Purpose of the Study:

  • To investigate the association between host genetics and subclinical atherosclerosis in HIV-infected individuals on HAART.
  • To identify specific genetic variations (SNPs and CNVs) linked to carotid intima-media thickness (cIMT) as a measure of atherosclerosis.

Main Methods:

  • A genome-wide association study (GWAS) was conducted on 177 HIV-positive Caucasian males from the FRAM Study.
  • Carotid intima-media thickness (cIMT) was measured using B-mode ultrasound.
  • Single nucleotide polymorphisms (SNPs) and Copy Number Variants (CNVs) were analyzed, with regression analyses performed to assess associations with cIMT, adjusting for relevant covariates.

Main Results:

  • Two single nucleotide polymorphisms (SNPs), rs2229116 and rs7177922, within the ryanodine receptor (RYR3) gene on chromosome 15 showed a significant association with common cIMT (P < 1.61 x 10^-7).
  • These SNPs are in tight linkage disequilibrium and represent a functional missense polymorphism.
  • The RYR gene family is implicated in cardiovascular disease etiology and can be regulated by HIV TAT protein.

Conclusions:

  • A functional single nucleotide polymorphism (SNP) in the RYR3 gene is associated with increased common carotid intima-media thickness in HIV-infected individuals undergoing HAART.
  • This finding highlights RYR3 as a biologically plausible candidate gene contributing to atherosclerosis in the context of HIV infection and treatment.
Abstract

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