Evidence has recently revealed that patients with vitiligo are shown to have elevated total Homocysteine (Hcy). As MTHFR is one of the main enzymes that regulates HCy metabolism, it is hypothesized by the authors that polymorphisms to these genes could contribute to vitiligo development. 1000 Chinese patients with vitiligo matched with 1000 healthy controls were tested for MTHFR C677T and A1298C genotypes. It was found the presence of the T allele in the C677T genotype was associated with a significantly reduced risk for vitiligo, suggesting a protective effect. Vitiligo patients showed lower concentrations of MTHFR and therefore higher levels of Hcy when compared for controls. Patients with lowered levels of Hcy, higher MTHFR gene activity or a no risk genotype (CT + TT) showed a significantly decreased risk of vitiligo.