Back to Search
Start Over
Evidence of epistatic interaction betweenDPP4andCCR6in patients with rheumatoid arthritis
- Source :
- Rheumatology. 55:2230-2236
- Publication Year :
- 2016
- Publisher :
- Oxford University Press (OUP), 2016.
-
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. 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 :
- Adult
Male
Receptors, CCR6
0301 basic medicine
Oncology
medicine.medical_specialty
Dipeptidyl Peptidase 4
Arthritis
Genome-wide association study
Logistic regression
Polymorphism, Single Nucleotide
Arthritis, Rheumatoid
03 medical and health sciences
0302 clinical medicine
Asian People
Rheumatology
Internal medicine
medicine
Humans
Lupus Erythematosus, Systemic
Genetic Predisposition to Disease
Pharmacology (medical)
Age of Onset
030203 arthritis & rheumatology
Systemic lupus erythematosus
business.industry
Epistasis, Genetic
Odds ratio
medicine.disease
030104 developmental biology
Case-Control Studies
Rheumatoid arthritis
Cohort
Physical therapy
Th17 Cells
Epistasis
Female
business
Genome-Wide Association Study
Subjects
Details
- ISSN :
- 14620332 and 14620324
- Volume :
- 55
- Database :
- OpenAIRE
- Journal :
- Rheumatology
- Accession number :
- edsair.doi.dedup.....594e8df07a4f1b95dc18181faa27f2b2