Genetic polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) and risk of vitiligo in Han Chinese populations: a genotype-phenotype correlation study

Abstract

SummaryBackground Recent evidence has revealed an elevation of total homocysteine (tHcy) in patients with vitiligo. Methylenetetrahydrofolate reductase (MTHFR) is one of the main enzymes regulating homocysteine (Hcy) metabolism. Thus, polymorphisms of MTHFR could potentially contribute to the development of vitiligo by affecting MTHFR activity and tHcy levels. Objectives To evaluate the potential association between MTHFR polymorphisms and vitiligo susceptibility. Methods In total, 1000 patients with vitiligo and 1000 age-and sex-matched controls were enrolled in this hospital-based case-control study. Two single-nucleotide polymorphisms of the MTHFR gene (rs1801133 C>T and rs1801131 A>C) were selected and genotyped using polymerase chain reaction (PCR)-restriction fragment length polymorphism and allele-specific PCR, respectively. The MTHFR activity concentration and tHcy level in serum were measured by enzyme-linked immunosorbent assay. Results We found that allele T of rs1801133 in the MTHFR gene was associated with a significantly reduced risk of vitiligo (adjusted odds ratio 0Á58, 95% confidence interval 0Á43-0Á76, P < 0Á001). In addition, the patients with vitiligo had a lower activity concentration of MTHFR and higher level of tHcy than the controls. Correlation between these markers and the risk of vitiligo was also observed. Furthermore, the individuals with a no-risk genotype (CT + TT) of rs1801133 and higher activity concentration of MTHFR or lower level of tHcy had a significantly decreased risk of vitiligo. Conclusions Our data suggest that MTHFR gene polymorphisms may play a vital role in genetic susceptibility to vitiligo.

Methylenetetrahydrofolate reductase (MTHFR): could it be a small piece in vitiligo jigsaw puzzle?

“…Further, the findings reported by Chen et al . are supported by the previous functional study of the MTHFR 1801133 SNP, which showed that both homozygous and heterozygous rs1801133 variants exhibited high levels of MTHFR enzyme activity and rescued the biochemical phenotype of the MTHFR knockout cells …”

“…Vitiligo has been the subject of debate involving several hypotheses, oxidative stress being a major contributor for melanocyte cell death . Among the significant candidate genes for vitiligo Chen et al . followed an important gene methylenetetrahydrofolate reductase ( MTHFR ) by functionally correlating its variants with its enzyme activity and total homocysteine (tHcy) levels.…”

“…In this issue of the BJD , Chen et al . have addressed the genetic association of two well‐reported nonsynonymous single‐nucleotide polymorphisms (SNPs) of MTHFR : 1801133C>T and 1801131A>C, suggesting their association with vitiligo risk in the Han Chinese population along with the clinical significance of elevated Hcy levels for patients with vitiligo.…”

Studying the association between methylenetetrahydrofolate reductase (MTHFR) 677 gene polymorphism, cardiovascular risk and lichen planus

“…The results of the current study were in agreement with previous studies that proved an association between MTHFR gene polymorphism and various chronic inflammatory diseases, including psoriasis, Behcet's disease and vitiligo …”

“…The results of the current study were in agreement with previous studies that proved an association between MTHFR gene polymorphism and various chronic inflammatory diseases, including psoriasis, Behcet's disease and vitiligo. [24][25][26] The results of the present study revealed that folate deficiency and hyperhomocysteinemia have been associated with the TT mutant genotype. However, these findings were not significant (P>.05).…”