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Vitiligo is an acquired pigmentation disorder characterized by melanocyte loss via autoimmune mechanisms triggered by oxidative stress. Gene polymorphisms in antioxidant enzymes and immunomodulators such as catalase (CAT) and vitamin D receptor (VDR), respectively, have been linked to vitiligo in European and Asian populations. Our aim was to evaluate the role of CAT and VDR gene polymorphisms as well as CAT and vitamin D in nonsegmental vitiligo in Northwestern Mexicans.A total of 357 subjects, 173 nonsegmental vitiligo patients and 184 age-gender matched healthy controls, were genotyped by PCR-restriction fragment length polymorphism. CAT activity was determined in 39 patients and in 39 controls and vitamin D (VitD) levels in 35 individuals per group.CAT 419 C/T gene polymorphism was not informative, -89 A/T was associated with risk (P = 0.02), and 389 C/T conferred protection against vitiligo along with AT haplotype (P < 0.01 in both cases). VDR BsmI, ApaI, and TaqI gene polymorphisms were not associated with vitiligo, but BsmI was more prevalent in patients with Koebner phenomenon (P = 0.02). Serum CAT activity and VitD levels were lower in patients than in controls, but they showed no association with any vitiligo clinical characteristics neither with their gene polymorphisms.Our results suggest a role for CAT gene polymorphisms in vitiligo susceptibility in the Mexican population and a lack of association with VDR gene polymorphisms.