Department of Biochemistry, Faculty of Science, Sir Sayajirao Gaikwad Medical College, Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, 390002, India.
Br J Dermatol. 2013 Nov;169(5):1114-25. doi: 10.1111/bjd.12467.
It has been suggested that NLRP1 is involved in susceptibility to a wide range of autoimmune diseases including generalized vitiligo (GV). Genetic polymorphisms in the gene encoding NLRP1 (previously known as NALP1) have previously been shown to be associated with GV and there is speculation about their involvement in the regulation of NLRP1 expression.
To explore NLRP1 polymorphisms and investigate their association with NLRP1 mRNA expression and disease activity in patients with GV.
Polymerase chain reaction (PCR)-restriction fragment length polymorphism and TaqMan single nucleotide polymorphism (SNP) genotyping techniques were used to genotype NLRP1 A/G (rs2670660), T/C (rs6502867) and A/T (rs12150220) polymorphisms in 537 patients with GV and 645 controls in Gujarat. NLRP1 mRNA levels were measured in the whole blood of 122 patients with GV and 175 controls using real-time PCR.
The NLRP1 rs2670660 and rs6502867 polymorphisms were found to be in significant association with GV, minor alleles of these SNPs being prevalent in active cases of GV. The rs12150220 polymorphism was found have a marginal association with GV. The frequency of susceptible haplotype 'GCT' was significantly higher in patients with GV and increased the risk of vitiligo twofold. A significant increase in NLRP1 mRNA expression was observed in patients with GV and patients with active GV. NLRP1 mRNA expression was increased in patients with GV with the susceptible GG (rs2670660) and CC (rs6502867) genotypes. Patients with the susceptible GG (rs2670660) and CC (rs6502867) genotypes had early age of onset of GV. Moreover, patients in the age at onset group of 1-20 years showed increased expression of NLRP1 mRNA compared with the older age groups. Female patients showed a significant increase in NLRP1 mRNA and early age at onset of GV compared with male patients.
Our results suggest that NLRP1 rs2670660 and rs6502867 polymorphisms may be genetic risk factors for susceptibility to and progression of GV. The upregulation of NLRP1 mRNA in patients with susceptible genotypes advocates the crucial role of NLRP1 in GV.
已有研究表明 NLRP1 与多种自身免疫性疾病的易感性有关，包括泛发性白癜风（GV）。编码 NLRP1（以前称为 NALP1）的基因中的遗传多态性已被证明与 GV 相关，并且有人推测它们参与了 NLRP1 表达的调节。
探讨 NLRP1 多态性，并研究其与 GV 患者 NLRP1mRNA 表达和疾病活动的关系。
采用聚合酶链反应（PCR）-限制性片段长度多态性和 TaqMan 单核苷酸多态性（SNP）基因分型技术，对古吉拉特邦 537 例 GV 患者和 645 例对照的 NLRP1A/G（rs2670660）、T/C（rs6502867）和 A/T（rs12150220）多态性进行基因分型。采用实时 PCR 法检测 122 例 GV 患者和 175 例对照全血中的 NLRP1mRNA 水平。
发现 NLRP1rs2670660 和 rs6502867 多态性与 GV 显著相关，这些 SNP 的次要等位基因在 GV 的活动期病例中更为常见。rs12150220 多态性与 GV 有边缘关联。GV 患者中易感单倍型“GCT”的频率明显升高，使白癜风的风险增加两倍。GV 患者和活动期 GV 患者的 NLRP1mRNA 表达均显著增加。NLRP1mRNA 表达在易感 GG（rs2670660）和 CC（rs6502867）基因型的 GV 患者中增加。易感 GG（rs2670660）和 CC（rs6502867）基因型的患者发病年龄较早。此外，发病年龄在 1-20 岁的患者与年龄较大的患者相比，NLRP1mRNA 的表达增加。与男性患者相比，女性患者的 NLRP1mRNA 表达增加，发病年龄较早。
我们的结果表明，NLRP1rs2670660 和 rs6502867 多态性可能是 GV 易感性和进展的遗传危险因素。易感基因型患者 NLRP1mRNA 的上调表明 NLRP1 在 GV 中具有关键作用。
