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PLoS One. 2015 May 20;10(5):e0125497. doi: 10.1371/journal.pone.0125497. eCollection 2015.

Association of the Lipoprotein Receptor SCARB1 Common Missense Variant rs4238001 with Incident Coronary Heart Disease.

Author information

1
Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, United States of America; Department of Public Health Sciences, Biostatistics Section, University of Virginia, Charlottesville, Virginia, United States of America.
2
Department of Public Health Sciences, Biostatistics Section, University of Virginia, Charlottesville, Virginia, United States of America.
3
Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, United States of America.
4
Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States of America.
5
Department of Medicine, Johns Hopkins University School of Medicine, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
6
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi, United States of America.
7
Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, United States of America.
8
Department of Cell Biology, University of Connecticut Health Center, Farmington, Connecticut, United States of America.

Abstract

BACKGROUND:

Previous studies in mice and humans have implicated the lipoprotein receptor SCARB1 in association with atherosclerosis and lipid levels. In the current study, we sought to examine association of SCARB1 missense single nucleotide polymorphism (SNP) rs4238001 with incident coronary heart disease (CHD).

METHODS AND RESULTS:

Genotypes for rs4238001 were imputed for 2,319 White, 1,570 African American, and 1,292 Hispanic-American MESA participants using the 1,000 Genomes reference set. Cox proportional hazards models were used to determine association of rs4238001 with incident CHD, with adjustments for age, sex, study site, principal components of ancestry, body mass index, diabetes status, serum creatinine, lipid levels, hypertension status, education and smoking exposure. Meta-analysis across race/ethnic groups within MESA showed statistically significant association of the T allele with higher risk of CHD under a consistent and formally adjudicated definition of CHD events in this contemporary cohort study (hazard ratio [HR] = 1.49, 95% CI [1.04, 2.14], P = 0.028). Analyses combining MESA with additional population-based cohorts expanded our samples in Whites (total n = 11,957 with 871 CHD events) and African Americans (total n = 5,962 with 355 CHD events) and confirmed an increased risk of CHD overall (HR of 1.19 with 95% CI [1.04, 1.37], P = 0.013), in African Americans (HR of 1.49 with 95% CI [1.07, 2.06], P = 0.019), in males (HR of 1.29 with 95% CI [1.08, 1.54], P = 4.91 x 10(-3)) and in White males (HR of 1.24 with 95% CI [1.03, 1.51], P = 0.026).

CONCLUSION:

SCARB1 missense rs4238001 is statistically significantly associated with incident CHD across a large population of multiple race/ethnic groups.

PMID:
25993026
PMCID:
PMC4439156
DOI:
10.1371/journal.pone.0125497
[Indexed for MEDLINE]
Free PMC Article

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