Han Shi-Liang, Zhang Yun-Jing, Zhou Ming, Luan Chong, Wang Pan, Zhai Lifeng
1 Department of Orthopaedics and Zibo Central Hospital, Zibo, China.
2 Department of Nephrology, Zibo Central Hospital, Zibo, China.
Genet Test Mol Biomarkers. 2019 Feb;23(2):84-90. doi: 10.1089/gtmb.2018.0219. Epub 2019 Jan 28.
To investigate the relationship between single nucleotide polymorphisms (SNPs) of protease-activated receptor 2 (PAR-2) and the susceptibility to knee osteoarthritis (KOA) and synovial expression of inflammatory factors in the Chinese Han population.
Three hundred fifty KOA patients (KOA group) and 345 healthy volunteers (control group) were recruited for the study. Five milliliters of venous blood was taken from each subject to detect the PAR-2 rs1529505, rs631465, and rs2242991 locus genotypes. The expression of PAR-2 mRNA in the synovial tissue and the levels of matrix metalloproteinase (MMP-1), MMP-9, interleukin (IL)-6, and IL-1β in the joint effusion were detected in 205 KOA patients who had undergone joint replacement surgery.
The PAR-2 rs1529505 T allele and the rs2242991 G allele carriers had a higher risk of KOA (p < 0.001). The severity of KOA in patients with the PAR-2 rs1529505 and rs2242991 mutations were higher than in the wild-type controls (p < 0.05). The expression levels of the PAR-2 mRNA in wild types, heterozygotes, and homozygotes of the rs1529505 and rs2242991 loci increased in turn (p < 0.001). The levels of MMP-1, MMP-9, IL-6, and IL-1β in the synovial fluid of the PAR-2 rs1529505 and rs2242991 locus mutants were distinctly higher than those with the wild-type alleles (p < 0.01). There was no correlation between the rs631465 SNP and susceptibility to KOA, severity of KOA, nor levels of PAR-2 mRNA, MMP-1, MMP-9, IL-6, and IL-1β.
The PAR-2 SNPs rs1529505 and rs2242991 are associated with the susceptibility to KOA. KOA is more severe in patients harboring the T and G alleles of these two SNPs, respectively. The levels of inflammatory factors in synovial tissue and blood are higher than those in wild-type patients.
探讨蛋白酶激活受体2（PAR-2）单核苷酸多态性（SNP）与中国汉族人群膝骨关节炎（KOA）易感性及滑膜炎症因子表达之间的关系。
招募350例KOA患者（KOA组）和345例健康志愿者（对照组）进行研究。采集每位受试者5毫升静脉血，检测PAR-2 rs1529505、rs631465和rs2242991位点基因型。对205例行关节置换手术的KOA患者，检测其滑膜组织中PAR-2 mRNA表达及关节积液中基质金属蛋白酶（MMP-1）、MMP-9、白细胞介素（IL）-6和IL-1β水平。
PAR-2 rs1529505 T等位基因和rs2242991 G等位基因携带者患KOA的风险更高（p<0.001）。PAR-2 rs1529505和rs2242991突变患者的KOA严重程度高于野生型对照组（p<0.05）。rs1529505和rs2242991位点野生型、杂合子和纯合子的PAR-2 mRNA表达水平依次升高（p<0.001）。PAR-2 rs1529505和rs2242991位点突变体滑膜液中MMP-1、MMP-9、IL-6和IL-1β水平明显高于野生型等位基因者（p<0.01）。rs631465 SNP与KOA易感性、KOA严重程度以及PAR-２mRNA、MMP-1、MMP-9、IL-6和IL-1β水平均无相关性。
PAR-2 SNPs rs1529505和rs2242991与KOA易感性相关。分别携带这两个SNP的T和G等位基因的患者KOA更严重。滑膜组织和血液中炎症因子水平高于野生型患者。
