title: Lack of a strong association of CTLA-4 exon 1 polymorphism with the susceptibility to rheumatoid arthritis and systemic lupus erythematosus in Japanese: an association study using a novel variation screening method.
abstract: CTLA-4 is considered to be one of the attractive candidates for the susceptibility genes to rheumatic diseases. In the present study, the association of CTLA-4 polymorphism with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) was examined in the Japanese population using the case-control association analysis. Polymerase chain reaction-preferential homoduplex formation assay (PCR-PHFA) was applied for the screening of genetic variations and for the genotyping of a large number of samples. A greater proportion of Japanese patients with RA (44%) and SLE (44%) compared with healthy individuals (37%) had exon 1 49 G/G genotype, but the difference did not reach statistical significance. However, when the patients with RA and healthy individuals were stratified according to HLA-DRB1 alleles, a weakly significant increase of the positivity of CTLA-4 49G allele was observed in HLA-DRB1*0405-positive patients (87%) compared with DRB1*0405-positive healthy individuals (71%) (P = 0.014, odds ratio = 2.77). These results indicate that CTLA-4 exon 1 polymorphism does not contribute greatly to the susceptibility to RA and SLE, at least in Japanese, although the presence of CTLA4 49G allele could be a minor predisposing factor for RA in HLA-DRB1*0405-positive individuals. In addition, PCR-PHFA was shown to be useful for a mass screening of gene variations.
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Matsushita
authors.forename: N
authors.initials: N
authors.lastname: Tsuchiya
authors.forename: M
authors.initials: M
authors.lastname: Shiota
authors.forename: T
authors.initials: T
authors.lastname: Komata
authors.forename: K
authors.initials: K
authors.lastname: Matsuta
authors.forename: K
authors.initials: K
authors.lastname: Zama
authors.forename: T
authors.initials: T
authors.lastname: Oka
authors.forename: T
authors.initials: T
authors.lastname: Juji
authors.forename: A
authors.initials: A
authors.lastname: Yamane
authors.forename: K
authors.initials: K
authors.lastname: Tokunaga
mesh_terms: D000069594:Abatacept; D000483:Alleles; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D001172:Arthritis, Rheumatoid / Q000453:epidemiology / Q000235:genetics*; D060908:CTLA-4 Antigen; D005091:Exons; D020022:Genetic Predisposition to Disease; D006801:Humans; D018796:Immunoconjugates; D007564:Japan / Q000453:epidemiology; D008180:Lupus Erythematosus, Systemic / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D000069594:Abatacept