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- Title
Evidence of epistatic interaction between DPP4 and CCR6 in patients with rheumatoid arthritis.
- Authors
Rui-Xue Leng; Juan Liu; Xiao-Ke Yang; Bin Wang; Chao Zhang; Sha-Sha Tao; De-Guang Wang; Xiao-Mei Li; Xiang-Pei Li; Hai-Feng Pan; Dong-Qing Ye
- Abstract
Objective. A recent genome-wide association study identified that genetic variants in DPP4 and CCR6 are connected with a risk of RA in the Han Chinese population. The aim of this study was to estimate the epistatic interaction between DPP4 and CCR6 in RA. Methods. Two single-nucleotide polymorphisms identified in a Han Chinese genome-wide association study (rs12617656 in DPP4, rs1854853 in CCR6) were genotyped. Logistic regression was used to estimate the multiplicative interaction and the additive interaction was analysed by 2 x 2 factorial design. Results. A total of 1224 subjects (377 RA patients, 847 healthy controls) were included in the initial analysis. Additionally, 600 patients with lupus arthritis were included for comparison. Significant multiplicative interaction between DPP4 and CCR6 was observed in RA [codominant model: odds ratio (OR) = 1.49, P = 0.003]. The epistatic effect seems to be stronger in ACPA-positive RA (codominant model: OR = 1.66, P = 0.001). However, no significant multiplicative interactions were observed in ACPA-negative RA or lupus arthritis. Additive interaction analysis showed a significant epistatic effect, but only in ACPA-positive RA [attributable proportion due to interaction = 0.48 (95% CI 0.10, 0.85)]. A further replication study of an independent cohort (476 subjects) found similar results. Pooled results confirmed that there was significant interaction between DPP4 and CCR6 on both the multiplicative and additive scales. Conclusion. The study suggests that a genetic interaction between DPP4 and CCR6 is involved in RA susceptibility. Furthermore, these findings highlight Th17 cell response as an important contributor in the pathogenesis of RA.
- Subjects
CHINA; RHEUMATOID arthritis risk factors; ACADEMIC medical centers; ALLELES; CHI-squared test; CHINESE people; CONFIDENCE intervals; GENETIC polymorphisms; RESEARCH; RESEARCH funding; SYSTEMIC lupus erythematosus; MATHEMATICAL variables; LOGISTIC regression analysis; CASE-control method; DATA analysis software; DESCRIPTIVE statistics; ODDS ratio; GENOTYPES
- Publication
Rheumatology, 2016, Vol 55, Issue 12, p2230
- ISSN
1462-0324
- Publication type
Article
- DOI
10.1093/rheumatology/kew315