Complement Receptor 1 Gene Variants Are Associated with Erythrocyte Sedimentation Rate
Complement Receptor 1 Gene Variants Are Associated with Erythrocyte Sedimentation Rate
复制标题
DOI：
10.1016/j.ajhg.2011.05.019
复制
发表时间：
2011-07-15
影响因子：
9.8
通讯作者：
Chute, Christopher G.
中科院分区：
文献类型：
--
作者：
Kullo, Iftikhar J.;Ding, Keyue;Chute, Christopher G.
红细胞沉降率（ESR）是一种常用的急性期反应试验，是红细胞在体外1小时内沉降的速率。红细胞沉降的分子基础尚不清楚。为了确定与ESR相关的遗传变异，我们在电子病历和基因组学（eMERGE）网络中对7607名患者进行了全基因组关联研究。发现队列由来自马约诊所的1979名个体组成，复制队列由来自其余4个eMERGE位点的5628名个体组成。补体受体1基因（CR 1）中的非同义SNP rs6691117（瓦尔-> IIe）与ESR相关（发现队列p = 7 x 10（-12），复制队列p = 3 x 10（-14），合并队列p = 9 x 10（-24））。我们在CR 1中插补了61个SNP，与rs6691117连锁不平衡（r（2）= 0.74）中的“可能损害”SNP（rs 2274567，His -> Arg）也与ESR相关（发现p = 5 x 10（-11），复制p = 7 x 10（-17），组合队列p = 2 x 10（-25））。CR 1中的两个非同义SNPs靠近C3 b/C4 b结合位点，表明变体可能影响ESR的可能机制。总之，CR 1的遗传变异，它编码一种蛋白质，清除补体标记的炎症颗粒从循环中，影响个体间的ESR变化，突出了先天免疫途径和红细胞相互作用之间的关联。
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 x 10(-12), replication cohort p = 3 x 10(-14), combined cohort p = 9 x 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 x 10(-11), replication p = 7 x 10(-17), and combined cohort p = 2 x 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.