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. 2012 Aug;32(8):1991-9.
doi: 10.1161/ATVBAHA.112.249714. Epub 2012 May 24.

Association of SCARB1 variants with subclinical atherosclerosis and incident cardiovascular disease: the multi-ethnic study of atherosclerosis

Ani Manichaikul  1 , Adam C Naj, David Herrington, Wendy Post, Stephen S Rich, Annabelle Rodriguez
Affiliations

Association of SCARB1 variants with subclinical atherosclerosis and incident cardiovascular disease: the multi-ethnic study of atherosclerosis

Ani Manichaikul et al. Arterioscler Thromb Vasc Biol. 2012 Aug.

Abstract

Objective: We previously reported a statistically significant association of SCARB1 intronic single nucleotide polymorphism (SNP) rs10846744 with common carotid intimal-medial artery thickness in each of the 4 Multi-Ethnic Study of Atherosclerosis racial/ethnic groups (white, Chinese, black, and Hispanic).

Methods and results: Using an expanded sample of 7936 Multi-Ethnic Study of Atherosclerosis participants, phenotyped for measures of subclinical atherosclerosis, incident myocardial infarction, and cardiovascular disease, and genotyped through the SNP Health Association Resource project, we have now examined the genetic association of these phenotypes with 126 genotyped and imputed SCARB1 SNPs. We also performed stratified analyses to examine whether SCARB1 SNP effects differed by sex. Our analysis of the full Multi-Ethnic Study of Atherosclerosis cohort provides strong evidence for the association of rs10846744 with common carotid intimal-medial thickness (P=1.04E-4 in combined analysis of all 4 Multi-Ethnic Study of Atherosclerosis racial/ethnic groups). In sex-stratified analysis, we observed statistically significant association of rs10846744 with incident cardiovascular disease events in males (P=0.01). Examining analytical results from the Myocardial Infarction Genetics Consortium for replication, we observed further support for the association of rs10846744 with myocardial infarction.

Conclusions: The SCARB1 SNP, rs10846744, exerts a major effect on subclinical atherosclerosis and incident cardiovascular disease in humans.

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Conflict of interest statement

B. None of the authors report a financial conflict.

Figures

Figure 1:
Figure 1:
Summary of regional association for SNPs in the SCARB1 gene region with common IMT (modeled on a log scale): (A) Strength of association versus SNP position on chromosome 12 based on meta-analysis to combine results from the four MESA racial/ethnic groups; (B) Forest plot of effects (with 95% CIs) reported in stratified analysis of the four MESA racial/ethnic groups; and Strength of association versus SNP position on chromosome 12 based on stratified analysis of (C) Caucasians, (D) Chinese, (E) African Americans, and (F) Hispanic. In plots (A) and (C-F), genotyped SNPs are indicated as solid black dots, imputed SNPs as solid gray dots, the genotyped SNP rs10846744 as an open black diamond, and horizontal dashed gray lines indicate a conservative Bonferroni-threshold for statistical significance based on multiple testing of 126 SNPs.
See this image and copyright information in PMC

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