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


CONCLUSIONS
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.
Durst
Ronen
R
Department of Cardiology, Hadassah Hebrew University Medical Center, Jerusalem, Israel. rdurst@partners.org
Neumark
Yehuda
Y
Meiner
Vardiella
V
Friedlander
Yechiel
Y
Sharon
Nir
N
Polak
Arthur
A
Beeri
Ronen
R
Danenberg
Haim
H
Erez
Gilli
G
Spitzen
Shoshi
S
Ben-Avi
Liat
L
Leitersdorf
Eran
E
Lotan
Chaim
C
D000328:Adult; D000483:Alleles; D050197:Atherosclerosis / Q000235:genetics*; D017023:Coronary Angiography; D005091:Exons; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D051117:Scavenger Receptors, Class A / Q000235:genetics*
C495139:MSR1 protein, human; D051117:Scavenger Receptors, Class A