Genetic Variants Of The Macrophage Scavenger Receptor 1 Gene Are Associated With Coronary Artery Disease

Coronary artery disease (CAD), of which atherosclerosis is the single most important contributor, is a complex vascular disease that results from the interaction between genetic and environmental factors. CAD is one of the major causes of death in most countries, including China. Occurrence of CAD involves inherited, behavioural and environmental factors, whereby inflammatory processes play key roles through early lesion formation to unstable plaque rupture in the development of atherosclerosis, the main cause of CAD.The macrophage scavenger receptor A, encoded by MSR1, is a pattern recognition receptor primarily expressed in macrophages. It mediates the uptake of modified LDL into cell resulting in foam cell formation. MSR1 also contributes to atherosclerosis by influencing cell apoptosis and secretion of inflammatory products. MSR1 expression level in the peripheral blood mononuclear cells has been found specifically increased in patients with acute coronary syndrome, and provided a predictive marker for a reattack of a cardiovascular event. We therefore investigated associations of MSR1 polymorphisms in the prevalence of CAD. In this study, we sought to test whether genetic variants in the MSR1 gene alter susceptibility to CAD in Chinese population. We genotyped ten polymorphic sites in the MSR1 gene including rs416748, rs433235, rs13306541, rs11274081, rs33959637, rs3747531, rs3036811, rs12718376, rs4333601 and rs7840885 in a hospital-based case-control study with 402 CAD patients and 400 controls. Among the 10 SNPs selected, 8 SNPs were successfully genotyped and consistent with those expected from the Hardy-Weinberg equilibrium (P > 0.05), whereas 2 SNPs (rs3747531 and rs33959637) that deviated from Hardy-Weinberg equilibrium (P < 0.05) were removed from our further analysis. We found that allele frequencies for rs416748 and rs13306541 were markedly different between patients with CAD and unaffected control subjects. Specifically, the frequency of allele"A"of rs416748 (P < 0.001) and the frequency of allele"G"of rs13306541 (P = 0.002) were higher in case subjects than in control respectively. Furthermore, there were significant elevated risks for CAD among the genetic variants, even when adjusted for age, sex, BMI, smoking status and hypertension (adjusted per-allele OR = 1.56 , 95% CI: 1.28-1.90, P < 0.001 for rs416748; adjusted per-allele OR = 1.70, 95% CI: 1.27-2.27, P < 0.001 for rs13306541, respectively), compared with their wild-type genotypes. Stratification analyses were conducted to evaluate the potential association of genetic variants of SNPs with risk of CAD in subgroup populations. Variant allele of rs416748 (A) had stronger effect on female (adjusted OR = 2.56, 95% CI: 1.43–4.60, P = 0.002); subjects with age≥60 years (adjusted OR = 2.11, 95% CI: 1.38–3.22, P = 0.001); subjects with BMI < 24 (adjusted OR = 2.34, 95% CI: 1.38–3.99, P = 0.002); non-smokers (adjusted OR = 2.24, 95% CI: 1.47–3.40, P < 0.001) and subjects with no hypertension (adjusted OR = 2.34, 95% CI: 1.46–3.75, P < 0.001). The rs13306541-G allele had stronger effect on female (OR = 3.26, 95% CI: 1.40-7.59, P = 0.006) ; subjects with BMI < 24 (adjusted OR = 1.85, 95% CI: 1.05– 3.24, P = 0.032); smokers (adjusted OR = 2.89, 95% CI: 1.40–5.95, P = 0.004) and subjects with no hypertension (adjusted OR = 1.70, 95% CI: 1.01–2.85, P = 0.044). The rs7840885 A allele had stronger effect on subjects with BMI≥24 (adjusted OR = 1.67, 95% CI: 1.06–2.63, P = 0.028) and non-smokers (adjusted OR = 1.55, 95% CI: 1.02–2.35, P = 0.039).Our results suggest that genetic variants of MSR1 gene might be associated with increased risk of CAD in the Chinese population. Future investigations should focus on the potential mechanisms whereby mutations identified here integrate into atherogenesis.