2 research outputs found
A Candidate Gene Study Revealed Sex-Specific Association Between the <i>OLR1</i> Gene and Carotid Plaque
No full text
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.
</jats:sec
Carotid Plaque and Candidate Genes Related to Inflammation and Endothelial Function in Hispanics From Northern Manhattan
No full text
Background and Purpose—
The genetic influence on carotid atherosclerotic plaque is mostly unknown. This study examines the association between carotid plaque and single nucleotide polymorphisms in selected genes implicated in inflammation and endothelial function.
Methods—
A total of 43 genes (197 single nucleotide polymorphisms) involved in inflammation and endothelial function were interrogated in 287 Dominicans from the Northern Manhattan Study (mean age, 64±7 years; 58% women) who had undergone high-resolution B-mode ultrasound for examination of carotid plaque. Using an additive genetic model, multiple logistic regression analyses were conducted, a within-gene haplotype analysis was performed, and interactions between genes were examined. Results were validated in an independent set of 301 Dominicans.
Results—
Carotid plaque was present in 143 (47%) participants. Nine genes had at least 1 single nucleotide polymorphism associated (
P
≤0.01) with carotid plaque phenotypes:
TNF
,
NOS2A
,
IL6R
,
TNFSF4
,
PPARA
,
IL1A
,
TLR4
,
ITGA2
, and
HABP2
. Single nucleotide polymorphisms
in TNFSF4
,
PPARA
,
TLR4
,
ITGA2
, and
HABP2
were also implicated with the same carotid phenotype in the validation analysis. Haplotype analysis revealed an additional gene of interest,
VCAM1
.
Conclusions—
We report novel associations between variations in 10 genes involved in inflammation and endothelial function and carotid plaque phenotypes in a Dominican sample, with replication for 5 genes in an independent Dominican sample.
</jats:sec
