Associations of TRAF1/C5 rs10818488 and rs3761847 polymorphisms with genetic susceptibility to rheumatoid arthritis: a case-control study and updated meta-analysis.

The results on associations of tumor necrosis factor (TNF)-receptor associated factor 1/complement component 5 (TRAF1/C5) rs10818488 and rs3761847 polymorphisms with rheumatoid arthritis (RA) are controversial, thus this study was performed to examine whether the aforementioned polymorphisms were associated with RA in a Chinese population. Furthermore, an updated meta-analysis was conducted. The polymorphisms were genotyped in 328 Chinese RA patients and 449 healthy controls. Studies examining the association of TRAF1/C5 rs10818488 and/or rs3761847 polymorphism with RA were exhaustively searched. No significant difference in either genotype or allele distribution between RA patients and controls was found. The updated meta-analysis was conducted based on 19 articles including the present study. A significant association of RA with TRAF1/C5 rs10818488 polymorphism G allele in Europeans (OR = 0.843, 95% CI = 0.730-0.975, p = 0.021) and in Asians (OR = 1.070, 95% CI = 1.009-1.136, p = 0.024) was found. Additionally, a significant association of RA with TRAF1/C5 rs10818488 polymorphism G allele under the recessive model in Asians (OR = 1.129, 95% CI = 1.023-1.246, p = 0.016) and in Africans (OR = 0.657, 95% CI = 0.507-0.851, p = 0.001) was found. Only a borderline significant association of RA with TRAF1/C5 rs3761847 polymorphism A allele was found in Europeans. Non-significant associations of RA with TRAF1/C5 rs10818488 and rs3761847 polymorphisms were found in our study. The updated meta-analysis results demonstrate that TRAF1/C5 rs10818488 polymorphism is associated with RA in Europeans, Asians and Africans, and TRAF1/C5 rs3761847 polymorphism is associated with RA in Europeans with borderline significant evidence.

A study on associations of single-nucleotide polymorphisms within H19 and HOX transcript antisense RNA (HOTAIR) with genetic susceptibility to rheumatoid arthritis in a Chinese population.

OBJECTIVE: The purpose of our study was to examine whether the H19 rs2839698, rs217727, and HOX transcript antisense RNA (HOTAIR) rs12826786 polymorphisms were associated with genetic susceptibility to rheumatoid arthritis (RA) in a Chinese population. METHODS: A total of 777 participants were enrolled in this study, including 328 RA patients and 449 healthy controls. The H19 rs2839698, rs217727, and HOTAIR rs12826786 polymorphisms were detected by the ligase detection reaction-polymerase chain reaction (LDR-PCR) technology. RESULTS: No significant difference in genotype distribution between RA patients and healthy controls was found (P = 0.38 for rs2839698; P = 0.79 for rs217727; P = 0.39 for rs12826786). The difference in allele frequencies between RA patients and controls was also non-significant (rs2839698 T versus C, P = 0.23, odds ratio (OR) = 1.15, 95% confidence interval (CI) = 0.92-1.43; rs217727 C versus T, P = 0.55, OR = 1.07, 95% CI = 0.87-1.32; and rs12826786 T versus C, P = 0.32, OR = 1.14, 95% CI = 0.88-1.47). We have also evaluated the relationships of above-mentioned polymorphisms with risk of RA under dominant model and recessive model, but non-significant evidence was found. No significant evidence was detected for the relationships of H19 rs2839698, rs217727, and HOTAIR rs12826786 polymorphisms with risk of different serotypes of RA. CONCLUSIONS: Our results indicated that H19 rs2839698, rs217727, and HOTAIR rs12826786 polymorphisms might not be involved in the genetic background of RA in Chinese.

Association study of AFF1 rs340630 polymorphism with genetic susceptibility to rheumatoid arthritis in Chinese population.

This study was performed to examine whether the AF4/FMR2 family, member 1 (AFF1) rs340630 polymorphism is involved in the genetic background of rheumatoid arthritis (RA) in a Chinese population. Two different study groups of RA patients and controls (328 RA patients and 449 healthy controls in the first study group; 232 RA patients and 313 controls in the second study group) were included in our study. Overall, there was no significant difference in either genotype (P=0.71 and 0.64 in the first and second study group, respectively) nor allele (in the first study group: A vs G, P=0.65, OR=1.05, 95%CI=0.85-1.29; in the second study group: G vs A, P=0.47, OR=1.10, 95%CI=0.86-1.40) frequencies of AFF1 rs340630 polymorphism between RA patients and controls. Our study represents the first report assessing the association of AFF1 rs340630 polymorphism with RA risk. No significant evidence was found for the dominant or recessive models. Further case-control studies with larger sample sizes and fine-mapping studies are needed to clarify the role of AFF1 in the genetic basis of RA.

Interaction analysis between BLK rs13277113 polymorphism and BANK1 rs3733197 polymorphism, MMEL1/TNFRSF14 rs3890745 polymorphism in determining susceptibility to rheumatoid arthritis.

Two pairwise genetic interactions (B cell lymphocyte kinase (BLK) rs13277113,B cell scaffold protein with ankyrin repeats 1 (BANK1) rs3733197and BLK rs13277113 membrane metalloendopeptidase like 1 (MMEL1)/ tumor necrosis factor receptor superfamily member 14 (TNFRSF14) rs3890745) have been demonstrated in determining susceptibility to rheumatoid arthritis (RA) without replication, thus this study was performed to examine whether abovementioned genetic polymorphisms were associated with RA and further tests were performed to see whether aforementioned genetic interactions existed in RA among Chinese population. A total of 328 patients with RA and 449 healthy control subjects were included in the current study. The polymorphisms were genotyped using the ligase detection reaction-polymerase chain reaction (LDR-PCR) technology. The association of RA with each polymorphism was analyzed by multivariate logistic regression model. Interaction analysis was done by multiple methods. Significant difference in genotype distribution of BLK rs13277113 polymorphism between RA patients and healthy controls was found (p = 1.01 × 10-2). The major allele A of BLK rs13277113 polymorphism was significantly increased in RA patients compared with controls (OR = 1.36, 95% CI = 1.08-1.71, p = 9.27 × 10-3). Significant association of RA with the major allele A of BLK rs13277113 polymorphism under dominant model was also detected (OR = 2.74, 95% CI = 1.42-5.29, p = 2.73 × 10-3). However, we did not find significant association between neither BANK1 rs3733197 polymorphism nor MMEL1/TNFRSF14 rs3890745 polymorphism and RA. Non-significant evidence was found for neither additive nor multiplicative interaction for these two pairwise genetic polymorphisms (BLK rs13277113-BANK1 rs3733197; BLK rs13277113-MMEL1/TNFRSF14 rs3890745). Significant association of RA with G allele of BANK1 rs3733197 polymorphism was only found among individuals carrying A/A genotype of the BLK rs13277113 polymorphism (OR = 1.49, 95% CI = 1.01-2.18, p = .04). In summary, our results indicated that the BLK rs13277113 polymorphism was involved in the genetic background of RA in Chinese population and the association of BANK1 rs3733197 polymorphism with RA was dependent on the genotype of BLK rs13277113 polymorphism, highlighting B-cell response implicated in the pathogenesis of RA.

Association study of AFF1 rs340630 polymorphism with genetic susceptibility to rheumatoid arthritis in Chinese population

This study was performed to examine whether the AF4/FMR2 family, member 1 (AFF1) rs340630 polymorphism is involved in the genetic background of rheumatoid arthritis (RA) in a Chinese population. Two different study groups of RA patients and controls (328 RA patients and 449 healthy controls in the first study group; 232 RA patients and 313 controls in the second study group) were included in our study. Overall, there was no significant difference in either genotype (P=0.71 and 0.64 in the first and second study group, respectively) nor allele (in the first study group: A vs G, P=0.65, OR=1.05, 95%CI=0.85-1.29; in the second study group: G vs A, P=0.47, OR=1.10, 95%CI=0.86-1.40) frequencies of AFF1 rs340630 polymorphism between RA patients and controls. Our study represents the first report assessing the association of AFF1 rs340630 polymorphism with RA risk. No significant evidence was found for the dominant or recessive models. Further case-control studies with larger sample sizes and fine-mapping studies are needed to clarify the role of AFF1 in the genetic basis of RA.