Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.
Department of Dermatology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.
Int J Immunogenet. 2019 Oct;46(5):321-330. doi: 10.1111/iji.12429. Epub 2019 Jul 10.
Non-segmental vitiligo (NSV) is an autoimmune skin disease. Genetics plays a predominant part in disease pathogenesis. Nucleotide-binding and oligomerization domain (NOD)-like receptors and pyrin-containing protein (NLRP) and Toll-like receptors (TLR) are pattern recognition receptors in mediating innate immunity. They participate in presenting pathogens and mediating the immune responses. NLRP and TLRs are involved in mediating immune response in various dermatological diseases. Understanding the influence of genetic polymorphisms of NLRP and TLRs associated with immune homeostasis might help us to understand the complex etiopathogenesis of NSV. Thus, we aimed to study the association of NLRP-1 (rs2670660) and TLR-4 (rs4986790) and the synergistic effects on disease spectrum, disease activity of NSV in South Indian population. This research was designed as a case-control genetic study with 264 patients and 264 controls. Genotyping of NLRP-1 (rs2670660) and TLR-4 (rs4986790) was performed by Taqman 5' allele discrimination assay and ARMS-PCR. Plasma levels of proteins were measured by enzyme-linked immunosorbent assay (ELISA). A statistically significant difference was observed with the frequency of homozygous GG genotype of NLRP-1 (rs2670660) (17.8% in cases vs. 5.3% in controls) (p < 0.0001; OR-3.73; 95% CI-1.94-7.14). Allele G was significantly frequent in 38% of the cases than in controls with 30% (p = 0.004; OR-1.46; 95% CI-1.13-1.89). Plasma NLRP-1 level was significantly higher in patients compared to controls (p < 0.05). Amongst cases, the plasma NLRP-1 levels did not show any difference with respect to their genotypes (p > 0.05). In TLR-4 (rs4986790), no significant difference in the frequency of genotypes and allele between cases and controls (p = 0.80) was observed; nevertheless, plasma TLR-4 was analogous between cases and controls (p > 0.05). Influence of genotype on plasma TLR-4 showed no significant difference in TLR-4 levels between GG and ancestral genotype AA, whilst heterozygous AG genotype showed a significant increase of TLR-4 compared to AA and GG (p = 0.02) amongst NSV cases. The obtained results suggest that NLRP-1 (rs2670660), and not TLR-4 ((rs4986790), is associated with increased risk of NSV in South Indian population.
非节段性白癜风 (NSV) 是一种自身免疫性皮肤病。遗传在疾病发病机制中起着主要作用。核苷酸结合和寡聚结构域 (NOD)-样受体和含吡咯蛋白 (NLRP) 和 Toll 样受体 (TLR) 是介导固有免疫的模式识别受体。它们参与病原体的呈现和免疫反应的介导。NLRP 和 TLR 参与各种皮肤疾病的免疫反应调节。了解与免疫稳态相关的 NLRP 和 TLR 遗传多态性的影响，可能有助于我们理解 NSV 的复杂发病机制。因此，我们旨在研究 NLRP-1（rs2670660）和 TLR-4（rs4986790）的遗传多态性与南印度人群 NSV 疾病谱、疾病活动度的相关性。这项研究设计为病例对照遗传研究，纳入了 264 例患者和 264 例对照。通过 Taqman 5'等位基因鉴别分析和 ARMS-PCR 对 NLRP-1（rs2670660）和 TLR-4（rs4986790）进行基因分型。通过酶联免疫吸附试验 (ELISA) 测量蛋白的血浆水平。 NLRP-1(rs2670660) 纯合 GG 基因型的频率（病例组 17.8%，对照组 5.3%）存在统计学显著差异（p<0.0001；OR-3.73；95%CI-1.94-7.14）。等位基因 G 在 38%的病例中明显比对照组中 30%更常见（p=0.004；OR-1.46；95%CI-1.13-1.89）。与对照组相比，患者的 NLRP-1 水平明显升高（p<0.05）。在病例中，血浆 NLRP-1 水平与其基因型无关（p>0.05）。在 TLR-4(rs4986790) 中，病例组和对照组在基因型和等位基因频率方面没有显著差异（p=0.80）；然而，病例组和对照组之间的血浆 TLR-4 相似（p>0.05）。基因型对血浆 TLR-4 的影响显示，在 TLR-4 水平方面，GG 基因型和祖先基因型 AA 之间没有显著差异，而杂合 AG 基因型与 AA 和 GG 相比，TLR-4 显著增加（p=0.02）。在 NSV 病例中。研究结果表明，NLRP-1（rs2670660）而非 TLR-4（rs4986790）与南印度人群 NSV 的发病风险增加相关。
