RYR3 gene variants in subclinical atherosclerosis among HIV-infected women in the Women's Interagency HIV Study (WIHS)

Aditi Shendre, Marguerite R. Irvin, Bradley E. Aouizerat, Howard W. Wiener, Ana I. Vazquez, Kathryn Anastos, Jason Lazar, Chenglong Liu, Roksana Karim, Nita A. Limdi, Mardge H. Cohen, Elizabeth T. Golub, Degui Zhi, Robert C. Kaplan, Sadeep Shrestha

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)666-672
Number of pages7
JournalAtherosclerosis
Volume233
Issue number2
DOIs
StatePublished - 2014

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Ryanodine Receptor Calcium Release Channel
Single Nucleotide Polymorphism
Atherosclerosis
HIV
Hispanic Americans
Genes
Haplotypes
Carotid Intima-Media Thickness
Meta-Analysis
Linear Models
Regression Analysis

Keywords

  • CCA
  • CIMT
  • HIV infection
  • RYR3
  • Single nucleotide polymorphisms
  • Subclinical atherosclerosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

Cite this

RYR3 gene variants in subclinical atherosclerosis among HIV-infected women in the Women's Interagency HIV Study (WIHS). / Shendre, Aditi; Irvin, Marguerite R.; Aouizerat, Bradley E.; Wiener, Howard W.; Vazquez, Ana I.; Anastos, Kathryn; Lazar, Jason; Liu, Chenglong; Karim, Roksana; Limdi, Nita A.; Cohen, Mardge H.; Golub, Elizabeth T.; Zhi, Degui; Kaplan, Robert C.; Shrestha, Sadeep.

In: Atherosclerosis, Vol. 233, No. 2, 2014, p. 666-672.

Research output: Contribution to journalArticle

Shendre, A, Irvin, MR, Aouizerat, BE, Wiener, HW, Vazquez, AI, Anastos, K, Lazar, J, Liu, C, Karim, R, Limdi, NA, Cohen, MH, Golub, ET, Zhi, D, Kaplan, RC & Shrestha, S 2014, 'RYR3 gene variants in subclinical atherosclerosis among HIV-infected women in the Women's Interagency HIV Study (WIHS)', Atherosclerosis, vol. 233, no. 2, pp. 666-672. https://doi.org/10.1016/j.atherosclerosis.2014.01.035
Shendre, Aditi ; Irvin, Marguerite R. ; Aouizerat, Bradley E. ; Wiener, Howard W. ; Vazquez, Ana I. ; Anastos, Kathryn ; Lazar, Jason ; Liu, Chenglong ; Karim, Roksana ; Limdi, Nita A. ; Cohen, Mardge H. ; Golub, Elizabeth T. ; Zhi, Degui ; Kaplan, Robert C. ; Shrestha, Sadeep. / RYR3 gene variants in subclinical atherosclerosis among HIV-infected women in the Women's Interagency HIV Study (WIHS). In: Atherosclerosis. 2014 ; Vol. 233, No. 2. pp. 666-672.
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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.",
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T1 - RYR3 gene variants in subclinical atherosclerosis among HIV-infected women in the Women's Interagency HIV Study (WIHS)

AU - Shendre, Aditi

AU - Irvin, Marguerite R.

AU - Aouizerat, Bradley E.

AU - Wiener, Howard W.

AU - Vazquez, Ana I.

AU - Anastos, Kathryn

AU - Lazar, Jason

AU - Liu, Chenglong

AU - Karim, Roksana

AU - Limdi, Nita A.

AU - Cohen, Mardge H.

AU - Golub, Elizabeth T.

AU - Zhi, Degui

AU - Kaplan, Robert C.

AU - Shrestha, Sadeep

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

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KW - CIMT

KW - HIV infection

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KW - Single nucleotide polymorphisms

KW - Subclinical atherosclerosis

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