Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA.
Am J Hum Genet. 2011 Jul 15;89(1):131-8. doi: 10.1016/j.ajhg.2011.05.019. Epub 2011 Jun 23.
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 (r(2) = 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.
红细胞沉降率（ESR）是一种常用于急性期反应的常规检测，它是指红细胞在体外 1 小时内沉降的速度。红细胞沉降的分子基础尚不清楚。为了鉴定与 ESR 相关的遗传变异，我们对电子病历和基因组学（eMERGE）网络中的 7607 名患者进行了全基因组关联研究。发现队列由来自梅奥诊所的 1979 名个体组成，复制队列由其余四个 eMERGE 站点的 5628 名个体组成。补体受体 1 基因（CR1）中的非同义 SNP(rs6691117，Val→Ile)与 ESR 相关（发现队列 p=7×10(-12)，复制队列 p=3×10(-14)，合并队列 p=9×10(-24)）。我们对 CR1 中的 61 个 SNP 进行了推断，与 rs6691117 连锁不平衡（r(2)=0.74）的“可能具有破坏性”的 SNP(rs2274567，His→Arg)也与 ESR 相关（发现 p=5×10(-11)，复制 p=7×10(-17)，合并队列 p=2×10(-25)）。CR1 中的两个非同义 SNP 位于 C3b/C4b 结合位点附近，这表明这些变异可能通过影响 ESR 来影响个体间的差异。综上所述，CR1 中的遗传变异，该基因编码一种从循环中清除补体标记的炎症颗粒的蛋白，影响 ESR 的个体间差异，突出了先天免疫途径与红细胞相互作用之间的关联。
