Document Type

Article

Disciplines

Life Sciences | Medicine and Health Sciences

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 = 4.91x10-3) 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.

Comments

PLoS One. 2015; 10(5): e0125497. Published online 2015 May 20. doi: 10.1371/journal.pone.0125497 PMID: 25993026 PMCID: PMC4439156

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