武汉云克隆科技股份有限公司

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 （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.

摘要：红细胞沉降率（ESR），一种常见的急性相位反应，是红细胞1小时内体外沉淀的速率。目前血沉的分子基础我们尚不清楚。为了研究与ESR相关的基因变异，我们在电子病案和基因组学（eMERGE）网络中对7607名患者中进行了一项全基因组关联研究。发现组由梅奥诊所的1979人组成，复制组由其余四个基因组学位点的5628人组成。补体受体1基因中的非同义SNP，rs6691117（Val→IIe），与红细胞沉降率有关（发现组p=7×10（-12），复制组p=3×10（-14），混合组p=9×10（-24））。我们推测CR1中有61个SNPs，以及一个“可能具有破坏性”的SNP（rs2274567，His→Arg）与rs 6691117的连锁不平衡（r（2）=0.74）也与血沉有关（发现组p=5×10（-11），重复组p=7×10（-17），混合组p=2×10（-25））。CR1中的两个非同义SNPs位于C3b/C4b结合位点附近，提示了变异体可能影响ESR的机制。补体受体1基因变异编码一种蛋白，清除有补体标记的炎症颗粒，影响ESR的个体间变异，强调天然免疫途径与红细胞相互作用的关系。

使用试剂原文信息：we measured CR1 levels by ELISA （USCN Life Science, Wuhan, China） in 50 patients with the genotype GG at rs669117 and 50 age- and sex-matched patients with genotypes AA and AG at that SNP.