The (CCTTT) n pentanucleotide repeat polymorphism in the inducible nitric oxide synthase gene promoter and the risk of psoriasis in Taiwanese

Abstract

Recently, genome-wide association studies identified a novel psoriasis susceptibility locus tagged by two single-nucleotide polymorphisms (SNPs) rs4795067 and rs28998802, both of which are in the intronic region of inducible nitric oxide synthase (iNOS) gene. This study aimed to assess the role of (CCTTT) n pentanucleotide repeat polymorphisms in the promoter region of iNOS gene in Chinese-Taiwanese patients with psoriasis. In total, 280 patients with psoriasis and 512 control subjects were analyzed for the presence of the iNOS microsatellite polymorphism by polymerase chain reactions. The alleles were classified as S and L alleles according to the number of (CCTTT) n repeats, with the alleles with ≤13 repeats designated as S and alleles with ≥14 repeats designated as L alleles. The distribution of allele frequencies and genotypes was significantly different between the control and psoriasis groups (P = 0.040, and 0.014, respectively). After adjustment for age, sex, body mass index, smoking, diabetes, and hypertension, carriers of the LL genotype were 0.38 (95% confidence interval 0.16-0.95) times less likely than non-carriers to have psoriasis (P = 0.038). The promoter assays demonstrated that the iNOS promoter activity increases in parallel with the repeat number of (CCTTT) n in HaCaT cells. Approximately 70% of the study subjects were genotyped for rs4795067 and rs28998802. The rs4795067 is in linkage disequilibrium with the microsatellite L/S allelic classification. The association of iNOS microsatellite with psoriasis is independent of these known iNOS variants. Our results suggest that the iNOS microsatellite may contribute to the genetic background of psoriasis in Chinese-Taiwanese patients.