title: Evidence of epistatic interaction between DPP4 and CCR6 in patients with rheumatoid arthritis.
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 × 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Epidemiology and Biostatistics, School of Public Health.|Anhui Provincial Laboratory of Population Health and Major Disease Screening and Diagnosis.
authors: Rui-Xue
authors: RX
authors: Leng
authors: Department of Epidemiology and Biostatistics, School of Public Health.|Anhui Provincial Laboratory of Population Health and Major Disease Screening and Diagnosis.
authors: Juan
authors: J
authors: Liu
authors: Department of Epidemiology and Biostatistics, School of Public Health.|Anhui Provincial Laboratory of Population Health and Major Disease Screening and Diagnosis.
authors: Xiao-Ke
authors: XK
authors: Yang
authors: Department of Epidemiology and Biostatistics, School of Public Health.|Anhui Provincial Laboratory of Population Health and Major Disease Screening and Diagnosis.
authors: Bin
authors: B
authors: Wang
authors: Department of Epidemiology and Biostatistics, School of Public Health.|Anhui Provincial Laboratory of Population Health and Major Disease Screening and Diagnosis.
authors: Chao
authors: C
authors: Zhang
authors: Department of Epidemiology and Biostatistics, School of Public Health.|Anhui Provincial Laboratory of Population Health and Major Disease Screening and Diagnosis.
authors: Sha-Sha
authors: SS
authors: Tao
authors: Department of Nephrology, Second Affiliated Hospital.
authors: De-Guang
authors: DG
authors: Wang
authors: Department of Rheumatology and Immunology, Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui, China.
authors: Xiao-Mei
authors: XM
authors: Li
authors: Department of Rheumatology and Immunology, Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui, China.
authors: Xiang-Pei
authors: XP
authors: Li
authors: Department of Epidemiology and Biostatistics, School of Public Health.|Anhui Provincial Laboratory of Population Health and Major Disease Screening and Diagnosis.
authors: Hai-Feng
authors: HF
authors: Pan
authors: Department of Epidemiology and Biostatistics, School of Public Health ydq@ahmu.edu.cn.|Anhui Provincial Laboratory of Population Health and Major Disease Screening and Diagnosis.
authors: Dong-Qing
authors: DQ
authors: Ye
mesh_terms: D000328:Adult; D017668:Age of Onset; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D044466:Asian People; D016022:Case-Control Studies; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics*; D004843:Epistasis, Genetic / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D054399:Receptors, CCR6 / Q000235:genetics*; D058504:Th17 Cells / Q000276:immunology
chemical_list: C106311:CCR6 protein, human; D054399:Receptors, CCR6; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4
keywords: CCR6; DPP4; genetic interaction; rheumatoid arthritis