title: Association of the CTLA-4 gene with rheumatoid arthritis in Chinese Han population.
abstract: Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is important for downregulation of T-cell activation, and CTLA-4 gene polymorphisms have been implicated as risk factors for rheumatoid arthritis (RA). Previous studies of the association between the +49 polymorphism of the CTLA-4 gene in RA have provided conflicting results. In order to determine association of the CTLA-4 gene with RA in Chinese Han population, we used denaturing gradient gel electrophoresis (DGGE) to genotype polymorphisms of four SNPs (MH30, +49, CT60 and JO31) of the CTLA-4 gene in 326 RA patients and 250 healthy controls. Furthermore, meta-analysis of all available studies relating +49 polymorphism to the risk of RA was performed to confirm the disease association. Among the SNPs examined, the genotype frequencies of CTLA-4 +49 and CT60 in RA patients differed significantly from controls (P=0.028 and 0.007). In addition, the distribution of four haplotypes constructed by these two SNPs was significantly different between patients and controls (chi(2)=10.58, d.f. =3, P=0.014). The meta-analysis also revealed that in both European and Asian populations, the CLTA-4 +49 G allele was associated with the risk of RA. These results suggested that the CTLA-4 gene might be involved in the susceptibility to RA in the Chinese Han population and both +49 and CT60 of CTLA-4 gene might be the causal variants in RA disease.
authors.affiliation: State Key Lab of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, PR China.
authors.forename: Cai
authors.initials: C
authors.lastname: Lei
authors.forename: Zhang
authors.initials: Z
authors.lastname: Dongqing
authors.forename: Shi
authors.initials: S
authors.lastname: Yeqing
authors.forename: Martin K
authors.initials: MK
authors.lastname: Oaks
authors.forename: Chen
authors.initials: C
authors.lastname: Lishan
authors.forename: Jin
authors.initials: J
authors.lastname: Jianzhong
authors.forename: Qian
authors.initials: Q
authors.lastname: Jie
authors.forename: Du
authors.initials: D
authors.lastname: Fang
authors.forename: Li
authors.initials: L
authors.lastname: Ningli
authors.forename: Han
authors.initials: H
authors.lastname: Xinghai
authors.forename: Ren
authors.initials: R
authors.lastname: Daming
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D002681:China; D005260:Female; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide
chemical_list: D020413:3' Untranslated Regions; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human