Inducible Nitric Oxide Synthase iNOS-954-G>C and Ex16+14-C>T Gene Polymorphisms and Susceptibility to Vitiligo in the Saudi Population.

Abstract

Objective: Vitiligo is an acquired pigmentary skin disorder with regional disappearance of melanocytes. Multigenic inheritance has been proposed in the pathogenesis of vitiligo. The present study aimed to investigate the possible association of inducible nitric oxide synthase polymorphisms iNOS-954-G/C (rs1800482 G>C) and iNOS-Ex16+14-C/T (rs2297518 C>T) with vitiligo in the Saudi population, if any.

Methods: We included 120 vitiligo cases and an equal number of age matched healthy controls. Polymerase chain reaction with restriction fragment length polymorphism method was used for the analysis of genetic polymorphisms.

Results: The heterozygous (GC), (GC + CC) combined genotype and variant allele; C allele of rs1800482 G>C were associated significantly (p < 0.005, after Bonferroni correction) with increased risk of vitiligo (OR = 3.46, 95% CI = 1.99-6.01, p = 0.001), (OR = 3.30, 95% CI= 1.93-5.65, p = 0.001) and (OR = 1.94, 95% CI = 1.31-2.87, p = 0.001) respectively. When GC genotype of rs1800482 G>C was co-inherited with common genotype (CC) and heterozygous genotype (CT) of rs2297518 C>T, the risk of vitiligo was significantly increased ((OR = 4.51, 95% CI = 2.18-9.33, p = 0.001) and (OR = 3.60, 95% CI = 1.61-8.01, p = 0.001)) respectively. None of the rs1800482 G>C and rs2297518 C>T genotypes and alleles have been associated with non-segmental vitiligo in terms of gender, age of onset, and types of vitiligo.

Conclusion: The heterozygous (GC), (GC+CC) combined genotype and variants allele; C allele of rs1800482 G>C, may cause overproduction of NO, which has been linked to melanocyte loss by increasing oxidative stress and decreasing melanocyte adhesion to the extracellular matrix components, and thus could be an associative risk factor for vitiligo.