背景:银屑病的全球患病率为1-3%,在不同的种族和地理区域观察到的差异。疾病易感性和对抗肿瘤坏死因子-α(TNFα)药物的反应提示了不同的遗传调节机制,其中可能包括NLR家族pyrin结构域包含3(NLRP3)多态性。NLRP3基因多态性的评价,银屑病患者血清CRP和TNFα水平及NLRP3(rs10754558)基因多态性,CRP和TNFα与疾病严重程度的关系及其作为银屑病对甲氨蝶呤和阿达木单抗反应的生物标志物的作用。该研究共有75名被诊断为寻常型银屑病的患者,将他们与75名健康个体的对照组进行比较。
结果:NLRP3基因型和等位基因分布在银屑病患者和对照组之间有非常显著的差异(P=0.002,0.004)。杂合子基因型GC(OR=3.67,95CI:1.75-7.68,P=0.0006),与牛皮癣的风险增加有关。此外,GC基因型与银屑病治疗无反应显著相关(OR=11.7,95CI:3.24-42.28,P=0.0002)。关于血清CRP和TNFα水平,银屑病患者和对照组之间存在高度统计学差异(P<0.0001),银屑病患者PASI50的应答者和非应答者之间也存在高度统计学差异(P<0.0001)。
结论:NLRP3(rs10754558)基因型GC与银屑病的严重形式和对银屑病药物的无应答有关。因此,NLRP3(rs10754558)基因多态性是银屑病患者预后的重要生物标志物。血清TNFα可用作银屑病患者对治疗反应的预测因子。仍然需要更多的研究来评估NLRP3基因多态性在与银屑病相关的遗传风险和治疗结果中的作用。
BACKGROUND: Psoriasis has a global prevalence of 1-3%, with variations observed across different ethnic groups and geographical areas. Disease susceptibility and response to anti-tumor necrosis factor-α (TNFα) drugs suggest different genetic regulatory mechanisms which may include NLR family pyrin domain containing 3 (NLRP3) polymorphism. Evaluation of the NLRP3 gene polymorphism, the serum level of CRP and TNFα in psoriasis patients and assessment of the NLRP3 (rs10754558) gene polymorphism, CRP and TNFα with disease severity and their role as biomarkers for response to
Methotrexate and Adalimumab in psoriasis. The study had a total of 75 patients diagnosed with psoriasis vulgaris, who were compared to a control group of 75 healthy individuals.
RESULTS: There was a highly significant difference in NLRP3 genotypes and alleles distribution between psoriasis patients and controls (P = 0.002,0.004). The heterozygote genotype GC (OR = 3.67,95%CI:1.75-7.68, P = 0.0006), was linked with increased risk of psoriasis. Additionally, The GC genotype was significantly associated with nonresponse to psoriasis therapy (OR = 11.7,95%CI:3.24-42.28, P = 0.0002). Regarding serum CRP and TNFα levels, there was a highly statistically significant difference between psoriasis patients and controls (P < 0.0001), and there was also a highly statistically significant difference between responders and non-responders in psoriasis patients regarding PASI 50 (P < 0.0001).
CONCLUSIONS: The NLRP3 (rs10754558) genotypes GC was associated with the severe form of psoriasis and with nonresponse to psoriasis medication. Therefore, NLRP3 (rs10754558) gene polymorphism is an important prognostic biomarker in psoriasis patients. The serum TNFα can be used as a predictor for response to therapy in psoriasis patients. More research for evaluation of role of the NLRP3 gene polymorphism in the genetic risks and treatment outcomes associated with psoriasis is still required.