中国人群中Fcγ受体IIB基因多态性与系统性红斑狼疮遗传易感性的关联——一项基于家系的关联研究。

Association of Fcgamma receptor IIB gene polymorphism with genetic susceptibility to systemic lupus erythematosus in Chinese populations--a family-based association study.

作者信息

Pan Faming, Zhang Kechun, Li Xiangpei, Xu Jianhua, Hao Jiahu, Ye Dongqing

机构信息

Department of Epidemiology & Biostatistics, School of Public Health, Anhui Medical University, 69 Meishan Road, Hefei, Anhui 230032, China.

出版信息

J Dermatol Sci. 2006 Jul;43(1):35-41. doi: 10.1016/j.jdermsci.2006.02.005. Epub 2006 Mar 10.

DOI:10.1016/j.jdermsci.2006.02.005

PMID:16531013

Abstract

BACKGROUND

The aim of this study was to investigate the role of FcgammaRIIB gene in susceptibility to systemic lupus erythematosus (SLE) using family-based association analysis method, and to examine possible haplotypes between two single-nucleotide polymorphisms.

OBJECTIVE

A total of 119 patients with SLE from 95 nuclear families, aged from 14 to 78 years, was selected according to 1997 criteria of American College of Rheumatology (ACR), In addition, 316 family members of these patients were also genotyped.

METHODS

A family-based association study was used to explore the relationship between gene polymorphism and SLE. We studied two single-nucleotide polymorphisms (SNPs) encoding non-synonymous substitution in the FcgammaRIIB gene with respect to genetic susceptibility to SLE. The FcgammaRIIB gene was genotyped by restriction fragment length polymorphism (RFLP) method.

RESULTS

Among 119 SLE patients, the frequencies of FcgammaRIIB-C50T CC, CT and TT genotypes were 12.7%, 60.7% and 26.6%, respectively. The frequencies of FcgammaRIIB-T225C TT, TC and CC genotypes were 8.1%, 61.3% and 30.6%, respectively. Four haplotypes, 50T-225C (34.1%), 50C-225C (27.7%), 50T-225T (19.7%) and 50C-50T (18.5%) were reconstructed. Univariate (single-marker) family-based association tests (FBATs) demonstrated that variant alleles at two SNPs, rs10917661 and rs1050501, in exons 2 and 5 of FcgammaRIIB gene were significantly associated with genetic susceptibility to SLE in additive model (exon 2, Z=3.444, P=0.00057; exon 5, Z=3.707, P=0.00020), respectively. Transmission/disequilibrium test (TDT) and sibship disequilibuium test (SDT) analysis showed an excess of the alleles of T (C50T) and C (T225/C) from heterozygous parents to affected offspring (chi(2)=10.88, P=0.0013; chi(2)=7.14, P=0.0105, respectively). Furthermore, the haplotype-specific FBATs showed 50T-225C (34.1%) haplotype was more frequently transmitted in SLE than other haplotypes (Z=3.539, P=0.00042).

CONCLUSIONS

Our findings provide strong evidence suggesting the FcgammaRIIB-50T-225C haplotype might be the susceptible factor of SLE in Chinese population.

摘要

背景

本研究旨在采用基于家系的关联分析方法，探讨FcγRIIB基因在系统性红斑狼疮（SLE）易感性中的作用，并检测两个单核苷酸多态性之间可能存在的单倍型。

目的

根据美国风湿病学会（ACR）1997年的标准，选取95个核心家庭中的119例SLE患者，年龄在14至78岁之间。此外，还对这些患者的316名家庭成员进行了基因分型。

方法

采用基于家系的关联研究方法，探讨基因多态性与SLE之间的关系。我们研究了FcγRIIB基因中编码非同义替换的两个单核苷酸多态性（SNP）与SLE遗传易感性的关系。采用限制性片段长度多态性（RFLP）方法对FcγRIIB基因进行基因分型。

结果

在119例SLE患者中，FcγRIIB-C50T的CC、CT和TT基因型频率分别为12.7%、60.7%和26.6%。FcγRIIB-T225C的TT、TC和CC基因型频率分别为8.1%、61.3%和30.6%。重建了四种单倍型，分别为50T-225C（34.1%）、50C-225C（27.7%）、50T-225T（19.7%）和50C-50T（18.5%）。单变量（单标记）基于家系的关联检验（FBAT）表明，FcγRIIB基因第2外显子和第5外显子中的两个SNP，即rs10917661和rs1050501的变异等位基因，在加性模型中分别与SLE的遗传易感性显著相关（第2外显子，Z = 3.444，P = 0.00057；第5外显子，Z = 3.707，P = 0.00020）。传递/不平衡检验（TDT）和同胞不平衡检验（SDT）分析显示，杂合子父母向患病后代传递T（C50T）和C（T225/C）等位基因的比例过高（分别为χ2 = 10.88，P = 0.0013；χ2 = 7.14，P = 0.0105）。此外，单倍型特异性FBAT显示，50T-225C（34.1%）单倍型在SLE中比其他单倍型更频繁地传递（Z = 3.539，P = 0.00042）。