title: RYR3 gene variants in subclinical atherosclerosis among HIV-infected women in the Women's Interagency HIV Study (WIHS).
abstract: BACKGROUND
  Single nucleotide polymorphisms (SNPs) in the Ryanodine receptor 3 (RYR3) gene are associated with common carotid intima media thickness (CCA cIMT) in HIV-infected men. We evaluated SNPs in the RYR3 gene among HIV-infected women participating in Women's Interagency HIV Study (WIHS).
  
  
  METHODS
  CCA cIMT was measured using B-mode ultrasound and the 838 SNPs in the RYR3 gene region were genotyped using the Illumina HumanOmni2.5-quad beadchip. The CCA cIMT genetic association was assessed using linear regression analyses among 1213 women and also separately among White (n=139), Black (n=720) and Hispanic (n=354) women after adjusting for confounders. A summary measure of pooled association was estimated using a meta-analytic approach by combining the effect estimates from the three races. Haploblocks were inferred using Gabriel's method and haplotype association analyses were conducted among the three races separately.
  
  
  RESULTS
  SNP rs62012610 was associated with CCA cIMT among the Hispanics (p=4.41×10(-5)), rs11856930 among Whites (p=5.62×10(-4)), and rs2572204 among Blacks (p=2.45×10(-3)). Meta-analysis revealed several associations of SNPs in the same direction and of similar magnitude, particularly among Blacks and Hispanics. Additionally, several haplotypes within three haploblocks containing SNPs previously related with CCA cIMT were also associated in Whites and Hispanics.
  
  
  CONCLUSIONS
  Consistent with previous research among HIV-infected men, SNPs within the RYR3 region were associated with subclinical atherosclerosis among HIV-infected women. Allelic heterogeneity observed across the three races suggests that the contribution of the RYR3 gene to CCA cIMT is complex, and warrants future studies to better understand regional SNP function.
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, United States.
authors.forename: Aditi
authors.initials: A
authors.lastname: Shendre
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, United States.
authors.forename: Marguerite R
authors.initials: MR
authors.lastname: Irvin
authors.affiliation: Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, United States; Department of Physiological Nursing, University of California, San Francisco, San Francisco, CA, United States.
authors.forename: Bradley E
authors.initials: BE
authors.lastname: Aouizerat
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, United States.
authors.forename: Howard W
authors.initials: HW
authors.lastname: Wiener
authors.affiliation: Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, United States.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Vazquez
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, United States.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Anastos
authors.affiliation: Department of Medicine, State University of New York, Downstate Medical Center, Brooklyn, NY, United States.
authors.forename: Jason
authors.initials: J
authors.lastname: Lazar
authors.affiliation: Department of Medicine, Georgetown University Medical Center, Washington, DC, United States.
authors.forename: Chenglong
authors.initials: C
authors.lastname: Liu
authors.affiliation: Atherosclerosis Research Unit, University of Southern California, Los Angeles, CA, United States.
authors.forename: Roksana
authors.initials: R
authors.lastname: Karim
authors.affiliation: Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, United States.
authors.forename: Nita A
authors.initials: NA
authors.lastname: Limdi
authors.affiliation: Department of Medicine, John Stroger Hospital and Rush University, Chicago, IL, United States.
authors.forename: Mardge H
authors.initials: MH
authors.lastname: Cohen
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
authors.forename: Elizabeth T
authors.initials: ET
authors.lastname: Golub
authors.affiliation: Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, United States.
authors.forename: Degui
authors.initials: D
authors.lastname: Zhi
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, United States.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kaplan
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, United States. Electronic address: sshrestha@uab.edu.
authors.forename: Sadeep
authors.initials: S
authors.lastname: Shrestha
mesh_terms: D000483:Alleles; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D050197:Atherosclerosis / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D044383:Black People / Q000235:genetics; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging; D059168:Carotid Intima-Media Thickness; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D005260:Female; D018740:Genetic Heterogeneity; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D012737:Sex Factors; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: D019380:Anti-HIV Agents; D019837:Ryanodine Receptor Calcium Release Channel
keywords: CCA; HIV infection; RYR3; Single nucleotide polymorphisms; Subclinical atherosclerosis; cIMT