Indhumathi Sundar, Rajappa Medha, Chandrashekar Laxmisha, Ananthanarayanan Palghat Hariharan, Thappa Devinder Mohan, Negi Vir Singh
Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.
Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.
Hum Immunol. 2017 Feb;78(2):209-215. doi: 10.1016/j.humimm.2016.12.006. Epub 2016 Dec 24.
Psoriasis is known to be associated with an up-regulation of T-helper (Th)-1 & Th-17 cytokines and a relative down-regulation of Th-2 and T-regulatory (T-reg) cytokines. Certain allelic variants of these cytokine genes may alter Th1/Th17 and Th2/T-reg balance and may be associated with the risk of psoriasis. Hence we aimed to determine the association of IL-4 (rs2243250), IL-10 (rs1800871 and rs1800896) and FOXP3 (rs3761548) gene polymorphisms with risk of psoriasis in South Indian Tamils.
A total of 360 cases of psoriasis and 360 healthy controls were recruited. The polymorphism in IL-4 (rs2243250) & IL-10 (rs1800871) were typed by ARMS-PCR and IL-10 (rs1800896) & FOXP3 (rs3761548) were typed by TaqMan 5'allele discrimination assay.
We observed that IL-4 (rs2243250) had a reduced risk of psoriasis, while the IL-10 (rs1800871) conferred an increased susceptibility to psoriasis, as compared with controls. However, IL-10 (rs1800896) and FOXP3 (rs3761548) gene polymorphisms were not associated with psoriasis risk. The plasma IL-4 levels was not different between the cases and controls, however the heterozygous CT genotype demonstrated significant high IL-4 levels. Plasma IL-10 levels were significantly increased in cases compared to controls, however none of the genotypes were associated with the plasma IL-10 levels.
Our results suggest that IL-4 (rs2243250) polymorphism is protective against psoriasis, while IL-10 (rs1800871) polymorphism confers increased risk of psoriasis in South Indian Tamils. Detection of these genetic variants as predictive risk factors may lead to the selection of patient-tailored therapy to maximize the effectiveness of therapy.
已知银屑病与辅助性T细胞(Th)-1和Th-17细胞因子上调以及Th-2和调节性T细胞(T-reg)细胞因子相对下调有关。这些细胞因子基因的某些等位基因变异可能会改变Th1/Th17和Th2/T-reg平衡,并可能与银屑病风险相关。因此,我们旨在确定白细胞介素-4(IL-4,rs2243250)、白细胞介素-10(IL-10,rs1800871和rs1800896)和叉头框蛋白3(FOXP3,rs3761548)基因多态性与南印度泰米尔人银屑病风险的关联。
共招募了360例银屑病患者和360名健康对照。采用扩增阻滞突变系统聚合酶链反应(ARMS-PCR)对IL-4(rs2243250)和IL-10(rs1800871)的多态性进行分型,采用TaqMan 5'等位基因鉴别分析对IL-10(rs1800896)和FOXP3(rs3761548)进行分型。
我们观察到,与对照组相比,IL-4(rs2243250)降低了银屑病风险,而IL-10(rs1800871)增加了患银屑病的易感性。然而,IL-10(rs1800896)和FOXP3(rs3761548)基因多态性与银屑病风险无关。病例组和对照组的血浆IL-4水平无差异,但杂合子CT基因型的IL-4水平显著较高。与对照组相比,病例组的血浆IL-10水平显著升高,但没有一种基因型与血浆IL-10水平相关。
我们的结果表明,IL-4(rs2243250)多态性对银屑病具有保护作用,而IL-10(rs1800871)多态性增加了南印度泰米尔人患银屑病的风险。检测这些基因变异作为预测风险因素可能会导致选择针对患者的个性化治疗,以最大限度地提高治疗效果。