Complement receptor 1 gene variants are associated with erythrocyte sedimentation rate

Iftikhar J. Kullo, Keyue Ding, Khader Shameer, Catherine A. McCarty, Gail P. Jarvik, Joshua C. Denny, Marylyn D. Ritchie, Zi Ye, David R. Crosslin, Rex L. Chisholm, Teri A. Manolio, Christopher G. Chute

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

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 hr. The molecular basis of erythrocyte sedimentation is unknown. To identify genetic variants associated with ESR, we carried out a genome-wide association study of 7607 patients in the Electronic Medical Records and Genomics (eMERGE) network. 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. A nonsynonymous 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, combined cohort p = 9 × 10-24). 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 nonsynonymous 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, which encodes a protein that clears complement-tagged inflammatory particles from the circulation, influences interindividual variation in ESR, highlighting an association between the innate immunity pathway and erythrocyte interactions.

Original languageEnglish (US)
Pages (from-to)131-138
Number of pages8
JournalAmerican journal of human genetics
Volume89
Issue number1
DOIs
StatePublished - Jul 15 2011

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Kullo, I. J., Ding, K., Shameer, K., McCarty, C. A., Jarvik, G. P., Denny, J. C., Ritchie, M. D., Ye, Z., Crosslin, D. R., Chisholm, R. L., Manolio, T. A., & Chute, C. G. (2011). Complement receptor 1 gene variants are associated with erythrocyte sedimentation rate. American journal of human genetics, 89(1), 131-138. https://doi.org/10.1016/j.ajhg.2011.05.019