Association of CTLA4 gene A-G polymorphism with rheumatoid arthritis in Chinese

Abstract

The aim of this study was to investigate the allelic association of a single nucleotide polymorphism in exon 1 of the cytotoxic T-lymphocyte antigen-4 (CTLA4) gene with rheumatoid arthritis (RA) in Chinese people. One hundred and eighty-six unrelated adults with RA and 203 randomly selected normal adults were studied. All were ethnic Chinese living in Taiwan. The CTLA4 A-G polymorphism was genotyped with a polymerase chain reaction (PCR) and digestion with the restriction enzyme BstEII. The genotype and allele frequencies of CTLA4 in patients with rheumatoid arthritis differed significantly from those of adult controls (P=0.022 and P=0.037, respectively). Genotype CTLA4 49 G/G and allele G were associated with an increased risk of RA (RR=1.72, 95% CI=1.15-2.57, P=0.008; RR=1.39, 95% CI=1.02-1.89, P=0.037, respectively), whereas genotype A/G and allele A were associated with protection against RA (RR=0.58, 95% CI=0.39-0.87, P=0.008 and RR=0.72, 95% CI=0.53-0.98, P=0.037, respectively). We concluded that, the CTLA4 49 A-G polymorphism is associated with RA in Chinese patients from Taiwan.

The CTLA4 + 49A/G and CT60 polymorphisms and chronic inflammatory arthropathies in Northern Ireland

“…Prior to this study, the G allele of the +49 A/G SNP was found to be associated with RA on seven occasions in five different ethnic populations (Cai et al, 2005;Lee et al, 2003;Vaidya et present study done in RA and JIA patients from a homogenous Northern Irish population reveals a unique, though relatively weak, association of the +49 A allele that has not been shown before in RA and JIA patients of other ethnic groups. To validate that the association of the +49 A allele with RA and JIA was not due to any peculiarities specific to the control group of healthy blood donors used, we genotyped a second control population consisting of healthy children of Northern Irish origin.…”

“…Initial comparison showed an increased frequency of the +49 A/G*A allele in the RA group (data not shown). As the majority of studies reporting disease association with this SNP hint towards increased frequency of the G allele (Cai et al, 2005;Lee et al, 2003;Vaidya et al, 2002;Yanagawa et al, 2000;Matsushita et al, 1999;Gonzalez-Escribano et al, 1999;Seidl et al, 1998), we wondered whether the association seen in our study could be due to any idiosyncratic characteristics specific to this control population (168 healthy blood donors). Therefore, + 49 A/G distribution in a second, distinctive Northern Irish control population consisting of 307 Northern Irish 12 to 15-year-old school children was compared to that in Group 1.…”

“…Haplotypes +49*G-CT60*G and +49*A-CT60*G were associated with disease (P = 0.0015 and P = 0.0425, respectively). Lee et al (2003) Taiwan 186 Abbreviations used: RA = rheumatoid arthritis, C = healthy controls.…”

“…The authors of the latter study also found the G allele of this SNP to be associated with lower mRNA levels of soluble CTLA-4 isoform, thus providing a rationale for a functional role in susceptibility to autoimmune diseases. Table 1 summarizes all the studies that have been done to date investigating the effects of CTLA-4 gene in RA (Cai et al, 2005;Lee et al, 2003;Rodríguez et al, 2002;Vaidya et al, 2002;Hadj Kacem et al, 2001;Yanagawa et al, 2000;Matsushita et al, 1999;Gonzalez-Escribano et al, 1999;Seidl et al, 1998;Orozco et al, 2004;Lee et al, 2002;Barton et al, 2000;Milicic et al, 2001). Results have been conflicting with some studies hinting towards association with RA, while others claiming to find no association at all.…”

Association of the CTLA-4 gene with rheumatoid arthritis in Chinese Han population

“…In rheumatoid arthritis, Vaidya has found in Caucasian the þ 49 G allele was positively associated, 9 and Lee et al, 21 has also reported similar results in Gaoshan people. Our study showed that þ 49 G allele was a risk factor of RA in Chinese Han population, which was in accord with above reports in other populations.…”