摘要
目的我国系统性红斑狼疮(systemic lupus erythematosus,SLE)发病率居世界首位,治疗属世界难题。SLE的发病机制尚不明确,许多研究表明,SLE患者红细胞补体受体1(complement receptor type 1,CR1)分子水平及功能低下,但未见研究对CR1基因与SLE遗传易感性的关联进行报道。文中旨在探讨红细胞CR1分子水平及其基因单核苷酸多态性(singlenucleotide polymorphisms,SNP)与SLE的关联。方法检测SLE患者(SLE组)及健康人(对照组)红细胞CR1分子水平及5个标签SNP位点基因型,比较对照组CR1基因各SNP位点基因型对应CR1分子水平的差异,以及SLE组和对照组组间红细胞CR1分子水平和CR1基因各SNP位点基因型、等位基因的分布差异,计算比值比(OR)及其95%CI。结果对照组CR1基因rs3818361C>T/TT基因型携带者红细胞CR1水平低于CC、CT基因型者(P<0.05),rs11118167T>C/TC、CC基因型携带者红细胞CR1水平低于TT基因型者(P<0.01),rs9429945C>T/CT、TT基因型携带者红细胞CR1水平低于CC基因型者(P<0.01)。SLE组CR1几何平均荧光强度比值(geometric mean fluorescence intensity ratio,GMFIR)低于对照组(P<0.01);有3个标签SNP位点与SLE发病关联(P<0.01或P<0.05),与非携带者比较,CR1-rs4844600G>A/GG基因型(OR:8.672,95%CI:3.864～19.462)及G等位基因(OR:7.419,95%CI:3.425～16.073)、CR1-rs3818361C>T/CC基因型(OR:1.872,95%CI:1.113～3.149)及C等位基因(OR:1.575,95%CI:1.067～2.325)、CR1-rs11118167T>C/TT基因型(OR:2.083,95%CI:1.065～4.071)及T等位基因(OR:1.941,95%CI:1.050～3.588)携带者患SLE风险增加。结论健康人CR1基因rs3818361C>T/TT基因型、rs11118167T>C/TC、CC基因型和rs9429945C>T/CT、TT基因型携带者红细胞CR1水平低于该SNP位点其他基因型携带者。SLE患者红细胞CR1分子水平降低,CR1基因rs4844600G>A、rs3818361C>T、rs11118167T>C等3个SNP位点与SLE发病关联,其易感基因型CR1-rs4844600G>A/GG、CR1-rs3818361C>T/CC和CR1-rs11118167T>C/TT与SLE患者CR1分子水平低无�
Objective The morbidity of systemic lupus erythematosus（SLE） in China occupies the first place in the world, and the therapy remains a difficult problem for the world. While the pathogenesis of SLE is unclear. Many researches have indicated that the level and function of complement receptor type 1 （ CR1 ） on erythrocytes in patients with SLE decreased. But the association of CR1 gene with the hereditary susceptibility to SLE has not been reported. This study was aim to investigate the association of erythro- cyte CR1 levels and its single nueleotide polymorphisms（SNP） in SLE. Methods The complement receptor type 1 （ CR1 ） levels on erythrocytes from 119 healthy controls and 117 SLE patients was measured by flow cytometer, and genotyping with five tag SNPs from CR1 gene was tested by the GenomeLabTM SNPstream~ 12-plex/48-plex genotyping system. The inter-group differences of CR1 levels a- mong every three genotypes from five SNPs of CR1 gene in healthy controls, and CR1 levels between SLE group and control group were compared bv CHISS 2005 software. The SPSS V13.0 software was utilized for the inter-~roun distributional differences comnarison ofgenotypes and alleles of SNPs from CR1 gene between SLE group and control group. The odds ratios （OR） and 95% confidence intervals （CI） for carriers vs non-carriers of genotypes or alleles were calculat- ed. Results The geometric mean fluorescence intensity ratios of CR1 （CR1-GMFIRs） in carriers of rs3818361C 〉 T/TY genotype, rsl 1118167T 〉 C/TC and CC genotypes, rs9429945C 〉 T/CT and TTgenotypes in healthy persons was lower than those with other genotypes of related SNPs（P 〈0.05, P 〈0.01 and P 〈0.01 ）. The CR1- GMFIR in SLE group was lower than that in control group（ P 〈 0.01 ）. There were statistical associations between 3 tag SNPs and SLE （P 〈 0.01 or P 〈 0.05 ）. When compared with noncarriers, the risk rates of developing SLE in carriers of CRl-rs4844600G 〉 A/GG genotype（OR：8. 672, 95% C1：3. 864 - 19. 462
出处
《医学研究生学报》
CAS
北大核心
2013年第7期729-733,共5页
Journal of Medical Postgraduates
关键词
系统性红斑狼疮
红细胞免疫
补体受体1
单核苷酸多态性
关联研究
Systemic lupus erythematosus
Erythrocyte immune
Complement receptor type 1
Single nucleotide polymor-phisms
Association study
