Increased risk for atherosclerosis of various macrophage scavenger receptor 1 alleles.

ABSTRACT

AIMS: Macrophage scavenger receptor 1 (MSR1) mediates the uptake of modified low density lipoprotein (LDL)-cholesterol. The significance of MSR1 in atherosclerosis development in animal models is uncertain. In this study we sought to determine the significance of MSR1 polymorphisms in its encoding gene in susceptibility to atherosclerosis. METHODS: We genotyped three polymorphic sites in the MSR1 gene including a 3-bp "TTA" insertion-deletion in intron 7 (rs3036811, Indel 7), an intron 5 SNP (rs33959637, IVS5-59), and a missense coding single nucleotide polymorphism (SNP) in exon 6 (rs3747531, P275A) in 136 nondiabetic Ashkenazi men under age 55 years (mean = 47.3 +/- 4.8 years) undergoing coronary angiography. Assessment of coronary disease was done by the number of segments with stenosis greater than 20% (coronary artery narrowing greater than 20% [CAGE > 20%]), greater than 50% (CAGE > 50%), and total number of diseased vessels. Linear regression modeling was used to define associations between atherosclerotic burden and MSR1 SNPs and haplotypes. RESULTS: Significant associations were noted between IVS5-59 and number of diseased vessels (p = 0.009) and CAGE > 20% (p = 0.017), which remained significant upon controlling for age, cholesterol level, hypertension, and smoking. CONCLUSION: This study demonstrates an association between MSR1 polymorphisms and atherosclerosis, suggesting that atherosclerotic risk associated with classic risk factors may be modified by MSR1 polymorphisms. These findings point to a significant role of MSR1 in atherosclerosis.