目的：类风湿性关节炎（RA）是一种复杂的炎症性自身免疫性疾病，系统表现，和许多易感遗传因素。P2X7受体是一个重要的配体门控通道，有助于许多生理过程，尤其是炎症。然而,基因变异可以改变P2X7受体的功能。因此,本研究旨在探讨P2X7基因多态性和表达对伊朗人群RA易感性的影响.
方法：我们登记了160名（145名女性，15名男性）RA患者和160名（142名女性，本研究中18名男性)健康个体。使用tetra扩增难治性突变系统-聚合酶链反应（TARMS-PCR）对rs1718119，rs2230912，rs2393799，rs28360457，rs35933842进行基因分型，并对rs1653624和rs3751143进行等位基因特异性PCR。此外，招募了44例新的RA病例和48名健康对照，以研究P2X7mRNA表达是否与RA易感性相关。
结果：结果显示，rs2393799在所有遗传模型中均显着增加RA的风险（p<0.05），而rs3751143处于优势状态(CC与AA,OR=0.49，95%CI=0.26-0.92），占优势(AC+CC，OR=0.59，95%CI=0.37-0.94），C等位基因（OR=0.63，95%CI=0.46-0.88），和rs2230912在共显性(AG与AA,OR=0.56，95%CI=0.34-0.94），占优势(AG+GGvs.AA,OR=0.59，95%CI=0.35-0.99)，占主导地位(AG与AA+GG,OR=0.57，95％CI=0.33-0.98）显着降低RA风险（p<0.05）。此外，rs1718119和rs1653624与RA的易感性无关（p>0.05），rs28360457和rs35933842在我们的研究中没有多态性。两组中P2X7的mRNA表达水平显示，与健康受试者（1.47±0.15，p<0.001）相比，RA中的P2X7基因显着上调（3.18±0.43）。
结论：我们的结果表明，在伊朗人群样本中，P2X7基因的rs2393799、rs3751143和rs2230912变异与RA的易感性相关。此外，我们的新RA患者中P2X7mRNA表达较高。P2X7受体已被认为是RA的潜在药理靶标。关键点•P2X7变体(rs2393799、rs2230912、rs3751143)与伊朗人群样本中的RA易感性相关。•rs2393799增加RA的风险，而rs2230912和rs3751143可降低RA的风险。•与对照相比,新的RA患者中P2X7表达显著上调。
OBJECTIVE: Rheumatoid arthritis (RA) is a complex inflammatory autoimmune disease with joint eruption, systemic manifestation, and numerous predisposing genetic factors. The
P2X7 receptor is an essential ligand-gated channel that contributes to many physiological processes, especially inflammation. However, genetic variations can alter the
P2X7 receptor function. Therefore, the present study aimed to explore the impact of P2X7 genetic polymorphisms and expression on susceptibility to RA in a sample of the Iranian population.
METHODS: We enrolled 160 (145 female, 15 male) RA patients and 160 (142 female, 18 male) healthy individuals in this study. Genotyping was performed using tetra amplification refractory mutation system-polymerase chain reaction (TARMS-PCR) for rs1718119, rs2230912, rs2393799, rs28360457, rs35933842, and allele-specific PCR for rs1653624 and rs3751143. Furthermore, 44 new cases of RA and 48 healthy controls were recruited to investigate whether P2X7 mRNA expression is associated with RA susceptibility.
RESULTS: The results revealed that the rs2393799 significantly increased the risk of RA in all genetic models (p<0.05), while rs3751143 in codominant (CC vs. AA, OR=0.49, 95% CI=0.26-0.92), dominant (AC+CC, OR=0.59, 95% CI=0.37-0.94), C allele (OR=0.63, 95% CI=0.46-0.88), and rs2230912 in codominant (AG vs. AA, OR=0.56, 95% CI=0.34-0.94), dominant (AG+GG vs. AA, OR=0.59, 95% CI=0.35-0.99), and overdominant (AG vs. AA+GG, OR=0.57, 95% CI=0.33-0.98) significantly decreased the RA risk (p<0.05). Furthermore, the rs1718119 and rs1653624 were not associated with susceptibility of RA (p>0.05), and rs28360457 and rs35933842 were not polymorphic in our study. The mRNA expression level of
P2X7 in both groups revealed that the
P2X7 gene was significantly upregulated in RA (3.18±0.43) compared to healthy subjects (1.47±0.15, p<0.001).
CONCLUSIONS: Our results suggest that rs2393799, rs3751143, and rs2230912 variants of the P2X7 gene are associated with RA\'s susceptibility in a sample of the Iranian population. Also,
P2X7 mRNA expression was higher in our new RA patients. The
P2X7 receptor has been considered as a potential pharmacologic target in RA. Key Points • P2X7 variants (rs2393799, rs2230912, rs3751143) were associated with RA susceptibility in a sample of the Iranian population. • rs2393799 increases the risk of RA, while rs2230912 and rs3751143 decrease the risk of RA. • P2X7 expression was significantly upregulated in new RA patients compared to controls.
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