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

doi:10.1016/j.atherosclerosis.2014.01.035

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 journal › Article › peer-review

7 Scopus citations

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 language	English (US)
Pages (from-to)	666-672
Number of pages	7
Journal	Atherosclerosis
Volume	233
Issue number	2
DOIs	https://doi.org/10.1016/j.atherosclerosis.2014.01.035
State	Published - Apr 2014

Keywords

CCA
CIMT
HIV infection
RYR3
Single nucleotide polymorphisms
Subclinical atherosclerosis

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.atherosclerosis.2014.01.035

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Shendre, A., Irvin, M. R., Aouizerat, B. E., Wiener, H. W., Vazquez, A. I., Anastos, K., Lazar, J., Liu, C., Karim, R., Limdi, N. A., Cohen, M. H., Golub, E. T., Zhi, D., Kaplan, R. C., & Shrestha, S. (2014). RYR3 gene variants in subclinical atherosclerosis among HIV-infected women in the Women's Interagency HIV Study (WIHS). Atherosclerosis, 233(2), 666-672. https://doi.org/10.1016/j.atherosclerosis.2014.01.035

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

@article{cdd9fb48fb724c7198e781018b6a97c4,

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. 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.",

keywords = "CCA, CIMT, HIV infection, RYR3, Single nucleotide polymorphisms, Subclinical atherosclerosis",

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

note = "Funding Information: Data in this manuscript were collected by the Women's Interagency HIV Study (WIHS) Collaborative Study Group with centers (Principal Investigators) at New York City/Bronx Consortium (Kathryn Anastos); Brooklyn, NY (Howard Minkoff); Washington DC Metropolitan Consortium (Mary Young); The Connie Wofsy Study Consortium of Northern California (Ruth Greenblatt); Los Angeles County/Southern California Consortium (Alexandra Levine); Chicago Consortium (Mardge Cohen); Data Coordinating Center (Stephen Gange). The WIHS is funded by the National Institute of Allergy and Infectious Diseases ( UO1-AI-35004 , UO1-AI-31834 , UO1-AI-34994 , UO1-AI-34989 , UO1-AI-34993 , and UO1-AI-42590 ) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development ( UO1-HD-32632 ). The study is co-funded by the National Cancer Institute , the National Institute on Drug Abuse , and the National Institute on Deafness and Other Communication Disorders . Funding is also provided by the National Center for Research Resources (UCSF-CTSI Grant Number UL1 RR024131 ) and NIH/NHLBI ( 1R01HL095140 & 1R01HL083760 ). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. ",

year = "2014",

month = apr,

doi = "10.1016/j.atherosclerosis.2014.01.035",

language = "English (US)",

volume = "233",

pages = "666--672",

journal = "Atherosclerosis",

issn = "0021-9150",

publisher = "Elsevier Ireland Ltd",

number = "2",

}

TY - JOUR

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

N1 - Funding Information: Data in this manuscript were collected by the Women's Interagency HIV Study (WIHS) Collaborative Study Group with centers (Principal Investigators) at New York City/Bronx Consortium (Kathryn Anastos); Brooklyn, NY (Howard Minkoff); Washington DC Metropolitan Consortium (Mary Young); The Connie Wofsy Study Consortium of Northern California (Ruth Greenblatt); Los Angeles County/Southern California Consortium (Alexandra Levine); Chicago Consortium (Mardge Cohen); Data Coordinating Center (Stephen Gange). The WIHS is funded by the National Institute of Allergy and Infectious Diseases ( UO1-AI-35004 , UO1-AI-31834 , UO1-AI-34994 , UO1-AI-34989 , UO1-AI-34993 , and UO1-AI-42590 ) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development ( UO1-HD-32632 ). The study is co-funded by the National Cancer Institute , the National Institute on Drug Abuse , and the National Institute on Deafness and Other Communication Disorders . Funding is also provided by the National Center for Research Resources (UCSF-CTSI Grant Number UL1 RR024131 ) and NIH/NHLBI ( 1R01HL095140 & 1R01HL083760 ). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.

PY - 2014/4

Y1 - 2014/4

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.

KW - CCA

KW - CIMT

KW - HIV infection

KW - RYR3

KW - Single nucleotide polymorphisms

KW - Subclinical atherosclerosis

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JO - Atherosclerosis

JF - Atherosclerosis

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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