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.

Keywords:

• vitiligo
• non-segmental
• genetic polymorphism
• rs1800482 G>C
• rs2297518 C>T
• nitric oxide
• nitric oxide synthase

Ethical Approval

Institutional ethical approval has been taken to conduct this research study.

Acknowledgment

The authors are thankful to Mohammad Asmari and S. Sadaf Rizvi for their help with laboratory work.

Disclosure

The authors declare that they have no conflict of interests in relation to this work.

Additional information

Funding

No external grants or other support were received for the conduction of this study.