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Association of NLRP 1 genetic variants and m RNA overexpression with generalized vitiligo and disease activity in a G ujarat population
Author(s) -
Dwivedi M.,
Laddha N.C.,
Mansuri M.S.,
Marfatia Y.S.,
Begum R.
Publication year - 2013
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.12467
Subject(s) - vitiligo , single nucleotide polymorphism , genotyping , genotype , nlrp1 , biology , minor allele frequency , haplotype , allele , genotype frequency , genetics , immunology , gene , apoptosis , programmed cell death , caspase
Summary 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 NALP 1 ) have previously been shown to be associated with GV and there is speculation about their involvement in the regulation of NLRP 1 expression. Objectives To explore NLRP 1 polymorphisms and investigate their association with NLRP 1 m RNA 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 NLRP 1 A/G (rs2670660), T/C (rs6502867) and A/T (rs12150220) polymorphisms in 537 patients with GV and 645 controls in G ujarat. NLRP 1 mRNA levels were measured in the whole blood of 122 patients with GV and 175 controls using real‐time PCR . Results The NLRP 1 rs2670660 and rs6502867 polymorphisms were found to be in significant association with GV , minor alleles of these SNP s 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 NLRP 1 m RNA expression was observed in patients with GV and patients with active GV . NLRP 1 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 NLRP 1 m RNA compared with the older age groups. Female patients showed a significant increase in NLRP 1 m RNA and early age at onset of GV compared with male patients. Conclusions Our results suggest that NLRP 1 rs2670660 and rs6502867 polymorphisms may be genetic risk factors for susceptibility to and progression of GV . The upregulation of NLRP 1 m RNA in patients with susceptible genotypes advocates the crucial role of NLRP1 in GV .