title: Association of NLRP1 genetic variants and mRNA overexpression with generalized vitiligo and disease activity in a Gujarat population.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  To explore NLRP1 polymorphisms and investigate their association with NLRP1 mRNA expression and disease activity in patients with GV.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biochemistry, Faculty of Science, Sir Sayajirao Gaikwad Medical College, Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, 390002, India.
authors.forename: M
authors.initials: M
authors.lastname: Dwivedi
authors.forename: N C
authors.initials: NC
authors.lastname: Laddha
authors.forename: M S
authors.initials: MS
authors.lastname: Mansuri
authors.forename: Y S
authors.initials: YS
authors.lastname: Marfatia
authors.forename: R
authors.initials: R
authors.lastname: Begum
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D017668:Age of Onset; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007194:India / Q000208:ethnology; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D000070576:NLR Proteins; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014820:Vitiligo / Q000208:ethnology / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D000070576:NLR Proteins; C427903:NLRP1 protein, human; D012333:RNA, Messenger