Goh Liuh Ling, Yong Mei Yun, See Wei Qiang, Chee Edward Yu Wing, Lim Pei Qi, Koh Ee Tzun, Leong Khai Pang
TTSH Research Laboratory, Clinical Research and Innovation Office, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore.
Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, Singapore, Singapore.
Rheumatol Int. 2017 Aug;37(8):1295-1302. doi: 10.1007/s00296-017-3762-x. Epub 2017 Jun 26.
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.
研究表明，类风湿关节炎（RA）的遗传风险因素在亚洲人群和白种人群之间存在显著差异。即使在亚洲人群中，NLRP1、PTPN22和PADI4的遗传贡献也一直存在争议。因此，我们试图梳理这些不同的研究结果，并确定这些提出的风险变异中是否有任何一个与新加坡华裔队列中RA的易感性、发病、疾病活动评分（DAS）活动和侵蚀相关。我们使用TaqMan分析法对500例抗环瓜氨酸肽抗体阳性（ACPA）的RA患者和500例健康对照者进行了NLRP1（rs878329和rs6502867）、PTPN22（rs2488457和rs6665194）以及PADI4（rs2240340）内的五个单核苷酸多态性（SNP）进行基因分型。NLRP1 rs878329的CC基因型和PADI4 rs2240340的TT基因型与RA易感性相关。基于亚洲人群先前的报告进行的荟萃分析证实了PADI4 rs2240340的T等位基因与RA的风险关联。PTPN22 rs6665194（-3508A>G）的GG基因型与RA风险显著降低相关。未发现NLRP1 rs6502867 T/C和PTPN22 rs2488457 G/C多态性有显著关联。五个SNP均与RA的临床特征无关。这项研究支持了PADI4 rs2240340的T等位基因与亚洲人RA的关联。首次证明了NLRP1 rs878329 G/C和PTPN22 rs6665194 A/G多态性的作用。我们还提出rs6665194有望成为不同种族间RA风险评估的候选指标。
