Search

Background: We have previously described the association between rheumatoid arthritis (RA) prevalence and the two mutY Homolog (E. coli) (MUTYH) SNPs (rs3219463 and rs3219476) among the Taiwanese population. This present study will aim to elucidate whether the SNPs can alter the expression of EGFR in the progression of RA., Methods: The cohort study included 368 Taiwan's Han Chinese RA patients and 364 healthy controls. Blood samples collected from the participants were analyzed to determine their serum MUTYH levels and to identify rs3219463 SNP of MUTYH from their genomic DNA., Results: Our data resulted in a statistically significant difference in genotype frequency distributions at rs3219463 for RA patients and controls (p < 0.0002). Also, the patients with G carrier at rs3219463 were less likely to suffer from painful joints (p < 0.006) and DAS28 scores (p < 0.003). Furthermore, the increase in serum level of MUTYH was also observed in RA patients (p < 0.005)., Conclusions: Our study showed that RA is associated with rs3219463 SNP in EGFR gene and an increased serum level of the MUTYH protein. These findings suggest MUTYH is worthy of further investigation as a therapeutic target for RA.

The involvement of uracil-DNA glycosylase (UNG) in the pathogenesis of cancer is well documented. In contrast, the role of this protein in rheumatoid arthritis (RA) development is not well defined, although previous studies suggest a possible link between autoimmune diseases and malignancy. Therefore, we aimed to examine whether there is a link between UNG genetic polymorphisms and RA. Our present study investigated the effects of UNG (rs3219218 and rs246079) single nucleotide polymorphisms (SNPs) on RA among Taiwan's Han Chinese population. Polymorphism of the UNG gene was analyzed in 192 controls and 183 RA patients. Genotyping for UNG SNPs was performed by restriction fragment length polymorphism assay. Our data confirmed statistically significant variations in genotype frequency distributions at rs246079 SNP between RA patients and controls (P = 3.05 × 10(-4)). The G allele at rs246079 SNP is a high-risk factor in developing RA (odds ratio [OR] = 1.77; 95% confidence interval [CI] = 1.290-2.42). A comparison of haplotype frequencies between the case and the control revealed that RA patients with the Ht2 haplotype are at additional risk for RA development (P = 0.042). Our data yielded new information on UNG polymorphisms associated with RA development and as RA molecular markers. The polymorphisms revealed by the present study merit further investigation.

The involvement of the epidermal growth factor receptor (EGFR) in the pathogenesis of cancer is well documented. In contrast, its role in rheumatoid arthritis (RA) development is not that well defined although previous studies suggested the possible link between autoimmune diseases and malignancy. Therefore, we aimed to examine whether there is a link between the EGFR genetic polymorphisms and the RA. Our study gauged the effects of EGFR (rs11543848 and rs17337023) single-nucleotide polymorphisms (SNPs) on RA among Taiwan's Han Chinese population. Polymorphism of EGFR gene was analyzed in 188 RA patients and 128 control subjects. Genotyping for EGFR SNPs was performed by restriction fragment length polymorphism (RFLP) assay. Our data confirmed statistically significant increased risk of RA development in subjects with A carrier at rs17337023 SNP (P < 0.0001), and subjects with A allele at rs17337023 SNP (odds ratio [OR] = 1.52; 95% confidence interval [CI] = 1.10-2.09). Furthermore, comparison of haplotype frequencies between patients and controls suggested GA and AT haplotypes were more "at-risk" for RA development (P < 0.0001 and P < 0.01, respectively). However, comparisons of the clinical features of RA patients according to different genotypes and haplotypes revealed no significant difference. In conclusion, our data yield the new information on EGFR polymorphisms (rs11543848 and rs17337023) with the susceptibility of RA development and polymorphism revealed by this study merit further investigation.

Unlabelled: It has been found that changes in CD4 expression and CD4+ T cell activity may influence tolerance or tissue destruction in autoimmune diseases and contribute to their risk. We examined whether an association of CD4 enhancer gene polymorphisms with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) exists., Methods: For study of the CD4 -11743A/C polymorphism, 192 patients with RA, 141 patients with SLE, and 96 normal controls participated. For the CD4 -10845A/G polymorphism, 191 patients with RA, 127 patients with SLE, and 92 controls participated. The polymorphism of the CD4 enhancer was examined with the polymerase chain reaction-restriction fragment length polymorphism method. Genotypic and allelic frequencies of the 3 groups of participants were compared. Genotype groups were also compared according to different clinical variables among the patients with RA and SLE., Results: For the CD4 -11743A/C polymorphism, patients with RA demonstrated significantly higher frequency of the C allele (p = 0.048); patients with SLE had significantly higher frequency of the CC genotype (p = 0.026), and lower frequency of the AC genotype (p = 0.013) compared with controls. For the CD4 -10845A/G polymorphism, patients with RA had significantly higher frequencies of the AA genotype (p = 0.047) and the A allele (p = 0.026); patients with SLE had significantly higher frequency of the AA genotype (p = 0.011) and A allele (p = 0.001), and lower frequency of the GG genotype (p = 0.003) compared with controls. A comparison of genotype groups according to different clinical variables revealed the association of the respective polymorphisms with mucosal ulcer lesions among patients with SLE., Conclusion: . Our results suggest that the genetic polymorphisms at the CD4 enhancer gene are associated with the risk of development of RA and SLE. They are also associated with mucosal ulcer lesions in patients with SLE.

Objective: The involvement of cytokines and chemokines in the pathogenesis of rheumatoid arthritis (RA) is well studied; however, the genetic bases behind this is not well understood. The aim of this study was to examine whether -572 G/C polymorphism in the IL-6 gene and 2767 A/G polymorphism in the 3'-untranslated region (UTR) of the IL-8 gene are associated with rheumatoid arthritis (RA)., Methods: We enrolled 199 RA patients and 130 normal controls. Polymerase chain reaction was used to identify the IL-6 -572G/C and IL-8 3'-UTR 2767A/G polymorphisms. The relationships between clinical manifestations of RA and the polymorphisms of each gene were investigated by comparing the genotypes among RA patients with different clinical variables., Results: We found no significant difference in the genotypic and allelic frequencies of the single nucleotide polymorphisms of IL-6 and IL-8 genes between RA patients and controls. Clinical characteristics such as age at onset, rheumatoid factor positivity, joint erosion and extra-articular manifestations were compared among patients with different genotypes of the IL-6 and IL-8 genes. We found that patients with IL-8 3'-UTR 2767AA genotype had a significantly younger age of onset of RA than patients without that genotype., Conclusion: The IL-6 -572 G/C and IL-8 3'-UTR 2767A/G polymorphisms are not associated with the risk of developing rheumatoid arthritis. However, the finding that patients with IL-8 3'-UTR 2767AA developed RA at a younger age suggests that this genotype may influence the etiopathology of RA in patients in Taiwan. Therefore, further single nucleotide polymorphism studies of this 3'UTR region may give more novel findings and understanding of the genetic basis of rheumatoid arthritis.

We investigated whether there is an association between polymorphism of the CYP17 gene and rheumatoid arthritis in Chinese patients in central Taiwan. Genomic DNA was extracted from the peripheral blood of 146 female and 47 male RA patients, as well as from 42 female and 59 male control subjects; restriction fragment length polymorphism (defined as the A1 and A2 alleles) was then determined. Clinical variables such as rheumatoid factor positivity, extra-articular manifestations, and joint erosion were also investigated for the RA patients. We found that more male RA patients had the A1 allele (P=0.019) and fewer female RA patients the A2 allele than control subjects (P=0.048). In male RA patients, A1 carriers showed more extra-articular manifestations (P=0.048). In female patients, a significant decrease in A2 carriers mainly occurred in the later-onset age group (P=0.024). This study suggests that the A2 allele may significantly decrease the overall risk of developing RA. In women, the protective effect of A2 mainly affects the older age group. In men, the clinical severity of RA may decrease in patients with the A2/A2 genotype.

The aim of this study was to investigate the association of tumor necrosis factor alpha (TNFalpha) gene promoter polymorphisms in Chinese patients with rheumatoid arthritis (RA) in central Taiwan. A total of 106 RA patients and 253 normal controls were studied. Polymerase chain reaction (PCR)-based restriction analysis was used to identify A/G polymorphism at position 308 in the promoter region of the TNFalpha, which is located at 6q21.3. For the genotype of TNFalpha-308 polymorphism, there was no statistically significant difference between RA patients and normal controls (Fisher's exact test, P=0.82). Additionally, no statistical association in the distribution of TNFalpha-308 polymorphism between rheumatoid factor (RF)-positive and -negative patients was noted. The lack of an association of TNFalpha-308 polymorphism with RA and RF in our study implies that TNFalpha-308 polymorphism cannot serve as a candidate gene marker for screening RA patients in Taiwan.