Complement receptor 1 gene variants are associated with erythrocyte sedimentation rate

Iftikhar Jan 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

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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

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Complement C1
Complement Receptors
Blood Sedimentation
Single Nucleotide Polymorphism
Genes
Electronic Health Records
Genomics
Erythrocytes
Acute-Phase Reaction
Genome-Wide Association Study
Linkage Disequilibrium
Innate Immunity
Complement System Proteins
Binding Sites

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Complement receptor 1 gene variants are associated with erythrocyte sedimentation rate. / Kullo, Iftikhar Jan; Ding, Keyue; Shameer, Khader; McCarty, Catherine A.; Jarvik, Gail P.; Denny, Joshua C.; Ritchie, Marylyn D.; Ye, Zi; Crosslin, David R.; Chisholm, Rex L.; Manolio, Teri A.; Chute, Christopher G.

In: American Journal of Human Genetics, Vol. 89, No. 1, 15.07.2011, p. 131-138.

Research output: Contribution to journalArticle

Kullo, IJ, Ding, K, Shameer, K, McCarty, CA, Jarvik, GP, Denny, JC, Ritchie, MD, Ye, Z, Crosslin, DR, Chisholm, RL, Manolio, TA & Chute, CG 2011, 'Complement receptor 1 gene variants are associated with erythrocyte sedimentation rate', American Journal of Human Genetics, vol. 89, no. 1, pp. 131-138. https://doi.org/10.1016/j.ajhg.2011.05.019
Kullo, Iftikhar Jan ; Ding, Keyue ; Shameer, Khader ; McCarty, Catherine A. ; Jarvik, Gail P. ; Denny, Joshua C. ; Ritchie, Marylyn D. ; Ye, Zi ; Crosslin, David R. ; Chisholm, Rex L. ; Manolio, Teri A. ; Chute, Christopher G. / Complement receptor 1 gene variants are associated with erythrocyte sedimentation rate. In: American Journal of Human Genetics. 2011 ; Vol. 89, No. 1. pp. 131-138.
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AU - Denny, Joshua C.

AU - Ritchie, Marylyn D.

AU - Ye, Zi

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