Abstract 13242: Complement Receptor 1 Gene Variants are Associated With Erythrocyte Sedimentation Rate
Introduction The erythrocyte sedimentation rate (ESR), a commonly performed test of the acute phase response, is the rate at which erythrocytes sediment in vitro in 1 h. A higher ESR is associated with an increased risk of adverse cardiovascular outcomes but the molecular basis of erythrocyte sedimentation is unknown.
Hypothesis We hypothesized that common genetic variants may influence inter-individual variation in ESR.
Methods To identify genetic variants associated with ESR, we carried out a genome-wide association study of 7607 patients of European ancestry in the Electronic Medical Records and Genomics (eMERGE) network (www.gwas.net). The discovery cohort consisted of 1979 individuals from the Mayo Clinic and the replication cohort consisted of 5628 individuals from the remaining four eMERGE sites. An efficient mixed-model association expedited (EMMAX) algorithm was used to correct for sample relatedness and cryptic population substructure in the genetic association analyses that adjusted for age, sex, hemoglobin level and site.
Results and conclusion A non-synonymous SNP ‘rs6691117’ (Val→IIe) in the complement receptor 1 gene (CR1) was associated with ESR (discovery cohort P=7×10-12, replication cohort P=3×10-14, and combined cohort P=9×10-24) (Table). We imputed 61 SNPs in CR1 and a ‘possibly damaging’ SNP (rs2274567, His→Arg) in linkage disequilibrium (r2=0.74) with rs6691117 was also associated with ESR (discovery P=5×10-11, replication P=7×10-17, and combined cohort P=2×10-25). The two non-synonymous SNPs in CR1 are near the C3b/C4b binding site, suggesting a possible mechanism by which the variants may influence ESR. In conclusion, genetic variation in CR1, a protein that clears complement-tagged inflammatory particles from the circulation, influences inter-individual variation in ESR, highlighting a novel association between the innate immunity pathway and erythrocyte interactions.
- © 2011 by American Heart Association, Inc.