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NLRP1, PTPN22 and PADI4 gene polymorphisms and rheumatoid arthritis in ACPA-positive Singaporean Chinese.
- Source :
-
Rheumatology international [Rheumatol Int] 2017 Aug; Vol. 37 (8), pp. 1295-1302. Date of Electronic Publication: 2017 Jun 26. - Publication Year :
- 2017
-
Abstract
- Studies have shown that the genetic risk factors for rheumatoid arthritis (RA) differ substantially between Asian and Caucasian populations. Even among Asian populations, the genetic contributions of NLRP1, PTPN22 and PADI4 have been controversial. Consequently, we sought to address these separate findings and determine whether any of these proposed risk variants are associated with RA susceptibility, onset, DAS activity and erosion in a Singaporean Chinese cohort. We genotyped five SNPs within NLRP1 (rs878329 and rs6502867), PTPN22 (rs2488457 and rs6665194), and PADI4 (rs2240340) in 500 anti-cyclic citrullinated peptide antibody-positive (ACPA) patients with RA and 500 healthy controls using TaqMan assays. The CC genotype of NLRP1 rs878329 and TT genotype of PADI4 rs2240340 were associated with RA susceptibility. The risk association of the T allele of PADI4 rs2240340 with RA was confirmed through a meta-analysis based on previous reports in Asian populations. The GG genotype of PTPN22 rs6665194 (-3508A>G) was associated with significantly reduced risk of RA. No significant association was found for NLRP1 rs6502867 T/C and PTPN22 rs2488457 G/C polymorphisms. None of the five SNPs was associated with RA's clinical features. This work supports the association of the T allele of PADI4 rs2240340 with RA in Asians. The roles of NLRP1 rs878329 G/C and PTPN22 rs6665194 A/G polymorphisms were demonstrated for the first time. We also propose rs6665194 to be a promising candidate for RA risk evaluation between ethnicities.
- Subjects :
- Adult
Aged
Arthritis, Rheumatoid immunology
Case-Control Studies
China
Enzyme-Linked Immunosorbent Assay
Female
Humans
Male
Middle Aged
NLR Proteins
Polymorphism, Single Nucleotide
Protein-Arginine Deiminase Type 4
Real-Time Polymerase Chain Reaction
Risk Factors
Young Adult
Adaptor Proteins, Signal Transducing genetics
Apoptosis Regulatory Proteins genetics
Arthritis, Rheumatoid genetics
Genetic Predisposition to Disease
Protein Tyrosine Phosphatase, Non-Receptor Type 22 genetics
Protein-Arginine Deiminases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1437-160X
- Volume :
- 37
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Rheumatology international
- Publication Type :
- Academic Journal
- Accession number :
- 28653215
- Full Text :
- https://doi.org/10.1007/s00296-017-3762-x