Association of cytosine–adenine repeat polymorphism of the estrogen receptor-β gene with rheumatoid arthritis symptoms

Abstract

The influence of the polymorphism of the estrogen receptor-beta gene, cytosine-adenine (CA) dinucleotide repeat in intron 6, in the occurrence of rheumatoid arthritis (RA) was investigated. Forty-seven RA patients and 36 control subjects with osteoarthritis (OA) were recruited. CA repeat polymorphism was examined using denaturing high-performance liquid chromatography (WAVE DNA Fragment Analysis System). The mean number of CA repeats was significantly higher in RA than in OA patients. Two groups were established: <or=21 repeats (short S), >or=22 repeats (long L); and 3 kinds of genotypes (SS, SL, LL) were found. In RA patients, the L allele frequency was higher (OR = 2.03; P <or= 0.05 Fisher's test) and more subjects carried the LL genotype (OR = 5.50; P <or= 0.05 Fisher's test) compared to OA patients. It was concluded that the presence of the L allele could be a risk factor for RA, although additional larger scale study is needed.

Association of a cytosine-adenine repeat polymorphism in the estrogen receptor &lt;i&gt;β&lt;/i&gt; gene with occurrence and severity of rheumatoid arthritis

“…In the present study, we ana-lyzed the CA repeat polymorphism by direct sequencing, a method typically used for the analysis of microsatellite polymorphisms. The mean CA repeat length observed for the RA patients was the same as that reported in a previous study [13]. Thus, neither the patient background nor the methods used for the analyses in the present study are likely to have resulted in the lack of association observed here.…”

“…We investigated the association of the CA repeat polymorphism in the intron 6 of the ERβ gene with RA and OA to follow up on the findings from a previous report [13]; however, our results did not reveal significant differences between RA and OA patients with respect to allele and genotype frequencies identified at this locus. Based on the patient characteristics ( Table 1), we evaluated the degree of severity of RA in the patients according to Ochi et al [15].…”

“…In addition, we categorized 2 allelic types according to the median number of CA repeats: ≦21 repeats (short allele, S), and ≧22 repeats (long allele, L). The cutoff value was based on that used in previous studies [10,12,13]. Based on these alleles, 3 genotypes (SS, SL and LL) were identified.…”

“…To date, only a single study has investigated the potential association between the ERβ CA repeat polymerphism and RA [13]. Wang et al [16] recently reported that shorter alleles (S, <23 repeats) were marginally associated with increased risk of systemic lupus eryhtematosus (SLE) compared with longer alleles (L, ≧23 repeats).…”

“…For example, a cytosine-adenine (CA) dinucleotide repeat in intron 6 and the single nucleotide polymorphism (SNP) rs1256049 (Rsa polymorphism) have been studied in the context of various human phenotypes, including osteoarthritis [10], bone mineral density [11], and climacteric disorder [12]. In RA, we previously reported that longer CA repeats in the intron 6 of ERβ and the GG genotype at SNP rs1256049 were potential risk factors for RA [13,14].…”