Aditi Shendre1, Marguerite R Irvin1, Bradley E Aouizerat2, Howard W Wiener1, Ana I Vazquez3, Kathryn Anastos4, Jason Lazar5, Chenglong Liu6, Roksana Karim7, Nita A Limdi8, Mardge H Cohen9, Elizabeth T Golub10, Degui Zhi3, Robert C Kaplan4, Sadeep Shrestha11. 1. Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, United States. 2. 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. 3. Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, United States. 4. Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, United States. 5. Department of Medicine, State University of New York, Downstate Medical Center, Brooklyn, NY, United States. 6. Department of Medicine, Georgetown University Medical Center, Washington, DC, United States. 7. Atherosclerosis Research Unit, University of Southern California, Los Angeles, CA, United States. 8. Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, United States. 9. Department of Medicine, John Stroger Hospital and Rush University, Chicago, IL, United States. 10. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States. 11. Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, United States. Electronic address: sshrestha@uab.edu.
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. DISCUSSION: 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.
BACKGROUND: Single nucleotide polymorphisms (SNPs) in the Ryanodine receptor 3 (RYR3) gene are associated with common carotid intima media thickness (CCA cIMT) in HIV-infectedmen. We evaluated SNPs in the RYR3 gene among HIV-infectedwomen 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. DISCUSSION: Consistent with previous research among HIV-infectedmen, SNPs within the RYR3 region were associated with subclinical atherosclerosis among HIV-infectedwomen. 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.
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