A candidate gene study revealed sex-specific association between the OLR1 gene and carotid plaque

Liyong Wang, Danielle Yanuck, Ashley Beecham, Hannah Gardener, Susan Slifer, Susan H Blanton, Ralph L Sacco, Tatjana Rundek

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

BACKGROUND AND PURPOSE - Sex differences have been recognized in stroke risk; however, the sex-dependent genetic contribution to stroke is unclear. We sought to examine the sex-dependent associations between genes involved in lipid metabolism and carotid atherosclerotic plaque, a subclinical precursor of stroke. METHODS - For the Genetic Determinant of Subclinical Carotid Disease study, 287 Dominicans ascertained through the Northern Manhattan Study were examined for carotid plaque using high-resolution ultrasound. Sixty-four single nucleotide polymorphisms (SNPs) in 11 lipid-related genes were genotyped. Plaque presence and plaque subphenotypes, including multiple, thick, irregular, and calcified plaque, were analyzed. First, the interaction between each SNP and sex was evaluated for association with each plaque phenotype using multiple logistic regression and controlling for age, smoking, and the main effects of sex and SNP. For SNPs with suggestive evidence for interaction with sex (P<0.1 for the interaction term), stratification analysis by sex was performed to evaluate the sex-specific association between the SNP and plaque phenotypes. RESULTS - The most compelling finding is with the missense SNP rs11053646 (K167N) in the OLR1 gene, which encodes lectin-like oxidized low-density lipoprotein receptor. Stratification analysis revealed a strong association between rs11053646 and all plaque phenotypes in women (OR, 2.44 to 5.86; P=0.0003 to 0.0081) but not in men (OR, 0.85 to 1.22; P=0.77 to 0.92). CONCLUSIONS - Genetic variation in genes involved in lipid metabolism may have sex-dependent effects on carotid plaque burden. Our findings provide a plausible biological basis underlying the sex difference in cardiovascular risk.

Original languageEnglish
Pages (from-to)588-592
Number of pages5
JournalStroke
Volume42
Issue number3
DOIs
StatePublished - Mar 1 2011

Fingerprint

Single Nucleotide Polymorphism
Genes
Stroke
Phenotype
Lipid Metabolism
Sex Characteristics
LDL Receptors
Atherosclerotic Plaques
Lectins
Logistic Models
Smoking
Lipids

Keywords

  • candidate genes
  • carotid plaque
  • lipids
  • OLR1
  • sex

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialized Nursing

Cite this

A candidate gene study revealed sex-specific association between the OLR1 gene and carotid plaque. / Wang, Liyong; Yanuck, Danielle; Beecham, Ashley; Gardener, Hannah; Slifer, Susan; Blanton, Susan H; Sacco, Ralph L; Rundek, Tatjana.

In: Stroke, Vol. 42, No. 3, 01.03.2011, p. 588-592.

Research output: Contribution to journalArticle

Wang, Liyong ; Yanuck, Danielle ; Beecham, Ashley ; Gardener, Hannah ; Slifer, Susan ; Blanton, Susan H ; Sacco, Ralph L ; Rundek, Tatjana. / A candidate gene study revealed sex-specific association between the OLR1 gene and carotid plaque. In: Stroke. 2011 ; Vol. 42, No. 3. pp. 588-592.
@article{e867f91553ba477292e58c4c7d7cdfbc,
title = "A candidate gene study revealed sex-specific association between the OLR1 gene and carotid plaque",
abstract = "BACKGROUND AND PURPOSE - Sex differences have been recognized in stroke risk; however, the sex-dependent genetic contribution to stroke is unclear. We sought to examine the sex-dependent associations between genes involved in lipid metabolism and carotid atherosclerotic plaque, a subclinical precursor of stroke. METHODS - For the Genetic Determinant of Subclinical Carotid Disease study, 287 Dominicans ascertained through the Northern Manhattan Study were examined for carotid plaque using high-resolution ultrasound. Sixty-four single nucleotide polymorphisms (SNPs) in 11 lipid-related genes were genotyped. Plaque presence and plaque subphenotypes, including multiple, thick, irregular, and calcified plaque, were analyzed. First, the interaction between each SNP and sex was evaluated for association with each plaque phenotype using multiple logistic regression and controlling for age, smoking, and the main effects of sex and SNP. For SNPs with suggestive evidence for interaction with sex (P<0.1 for the interaction term), stratification analysis by sex was performed to evaluate the sex-specific association between the SNP and plaque phenotypes. RESULTS - The most compelling finding is with the missense SNP rs11053646 (K167N) in the OLR1 gene, which encodes lectin-like oxidized low-density lipoprotein receptor. Stratification analysis revealed a strong association between rs11053646 and all plaque phenotypes in women (OR, 2.44 to 5.86; P=0.0003 to 0.0081) but not in men (OR, 0.85 to 1.22; P=0.77 to 0.92). CONCLUSIONS - Genetic variation in genes involved in lipid metabolism may have sex-dependent effects on carotid plaque burden. Our findings provide a plausible biological basis underlying the sex difference in cardiovascular risk.",
keywords = "candidate genes, carotid plaque, lipids, OLR1, sex",
author = "Liyong Wang and Danielle Yanuck and Ashley Beecham and Hannah Gardener and Susan Slifer and Blanton, {Susan H} and Sacco, {Ralph L} and Tatjana Rundek",
year = "2011",
month = "3",
day = "1",
doi = "10.1161/STROKEAHA.110.596841",
language = "English",
volume = "42",
pages = "588--592",
journal = "Stroke",
issn = "0039-2499",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - A candidate gene study revealed sex-specific association between the OLR1 gene and carotid plaque

AU - Wang, Liyong

AU - Yanuck, Danielle

AU - Beecham, Ashley

AU - Gardener, Hannah

AU - Slifer, Susan

AU - Blanton, Susan H

AU - Sacco, Ralph L

AU - Rundek, Tatjana

PY - 2011/3/1

Y1 - 2011/3/1

N2 - BACKGROUND AND PURPOSE - Sex differences have been recognized in stroke risk; however, the sex-dependent genetic contribution to stroke is unclear. We sought to examine the sex-dependent associations between genes involved in lipid metabolism and carotid atherosclerotic plaque, a subclinical precursor of stroke. METHODS - For the Genetic Determinant of Subclinical Carotid Disease study, 287 Dominicans ascertained through the Northern Manhattan Study were examined for carotid plaque using high-resolution ultrasound. Sixty-four single nucleotide polymorphisms (SNPs) in 11 lipid-related genes were genotyped. Plaque presence and plaque subphenotypes, including multiple, thick, irregular, and calcified plaque, were analyzed. First, the interaction between each SNP and sex was evaluated for association with each plaque phenotype using multiple logistic regression and controlling for age, smoking, and the main effects of sex and SNP. For SNPs with suggestive evidence for interaction with sex (P<0.1 for the interaction term), stratification analysis by sex was performed to evaluate the sex-specific association between the SNP and plaque phenotypes. RESULTS - The most compelling finding is with the missense SNP rs11053646 (K167N) in the OLR1 gene, which encodes lectin-like oxidized low-density lipoprotein receptor. Stratification analysis revealed a strong association between rs11053646 and all plaque phenotypes in women (OR, 2.44 to 5.86; P=0.0003 to 0.0081) but not in men (OR, 0.85 to 1.22; P=0.77 to 0.92). CONCLUSIONS - Genetic variation in genes involved in lipid metabolism may have sex-dependent effects on carotid plaque burden. Our findings provide a plausible biological basis underlying the sex difference in cardiovascular risk.

AB - BACKGROUND AND PURPOSE - Sex differences have been recognized in stroke risk; however, the sex-dependent genetic contribution to stroke is unclear. We sought to examine the sex-dependent associations between genes involved in lipid metabolism and carotid atherosclerotic plaque, a subclinical precursor of stroke. METHODS - For the Genetic Determinant of Subclinical Carotid Disease study, 287 Dominicans ascertained through the Northern Manhattan Study were examined for carotid plaque using high-resolution ultrasound. Sixty-four single nucleotide polymorphisms (SNPs) in 11 lipid-related genes were genotyped. Plaque presence and plaque subphenotypes, including multiple, thick, irregular, and calcified plaque, were analyzed. First, the interaction between each SNP and sex was evaluated for association with each plaque phenotype using multiple logistic regression and controlling for age, smoking, and the main effects of sex and SNP. For SNPs with suggestive evidence for interaction with sex (P<0.1 for the interaction term), stratification analysis by sex was performed to evaluate the sex-specific association between the SNP and plaque phenotypes. RESULTS - The most compelling finding is with the missense SNP rs11053646 (K167N) in the OLR1 gene, which encodes lectin-like oxidized low-density lipoprotein receptor. Stratification analysis revealed a strong association between rs11053646 and all plaque phenotypes in women (OR, 2.44 to 5.86; P=0.0003 to 0.0081) but not in men (OR, 0.85 to 1.22; P=0.77 to 0.92). CONCLUSIONS - Genetic variation in genes involved in lipid metabolism may have sex-dependent effects on carotid plaque burden. Our findings provide a plausible biological basis underlying the sex difference in cardiovascular risk.

KW - candidate genes

KW - carotid plaque

KW - lipids

KW - OLR1

KW - sex

UR - http://www.scopus.com/inward/record.url?scp=79952071989&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79952071989&partnerID=8YFLogxK

U2 - 10.1161/STROKEAHA.110.596841

DO - 10.1161/STROKEAHA.110.596841

M3 - Article

VL - 42

SP - 588

EP - 592

JO - Stroke

JF - Stroke

SN - 0039-2499

IS - 3

ER -