High incidence of MTHFR, CBS, and MTRR polymorphisms in vitiligo patients. Preliminary report in a retrospective study

Eur Rev Med Pharmacol Sci. 2019 Jan;23(2):471-478. doi: 10.26355/eurrev_201901_16858.


Objective: Vitiligo is a multifactorial polygenic disorder with a complex pathogenesis. It is related to both genetic and no genetic factors. The role of genetics is currently studied with several analytical approaches, such as genetic linkage, candidate gene association studies, genome-wide association studies (GWAS), deep DNA re-sequencing and gene expression studies. To date, there are no genetic traits directly related to vitiligo pathogenesis.

Patients and methods: 43 cases of vitiligo patients and 30 healthy donors recruited as control, were screened by assaying the biochemical molecules involved in the self-cells cytotoxicity (haptoglobin and homocysteine) and candidate genes involved in the regulatory process of the re-methylation cycles and transsulfuration. Candidate genes and their polymorphisms screened are methylene-tetrahydrofolate-reductase (MTHFR) C677T and A1298C; cystathionine-beta-synthase enzyme (CBS) I278T and Ins68bp; and methionine-synthase-reductase (MTRR) A66G.

Results: A peculiar genetic profile in vitiligo patients are defined: 11.6% of vitiligo patients shown polymorphic variant MTHFR 677TT vs. 3.3% of healthy donor MTHFR 677CC profile (p=0.0017); 14.0% of vitiligo patients shown CBS polymorphic variant 278TT vs. 3.3% of healthy donor 278II profile (p=0.0012); and 11.6% of vitiligo patients shown MTRR 66GG vs. 3.3% of healthy donor MTRR 677AA profile (p>0.0001).

Conclusions: This is the first study reporting the correlation between the polymorphic status of MTHFR C677T, CBS I278T, and MTRR A66G and vitiligo. The genetic screening of these polymorphisms could be useful for early detection of the inheritance risk factor in a subject carrying relatives with vitiligo. Although these data could suggest a kind of dysregulation, genetically based, of thiols production mechanisms. Based on these results, we have not been able to get hypothesis about the putative pathogenesis of vitiligo, and the precise cause remains unclear.

MeSH terms

  • Ceruloplasmin / analysis
  • Cystathionine beta-Synthase / genetics*
  • Cystathionine beta-Synthase / metabolism
  • Female
  • Ferredoxin-NADP Reductase / genetics*
  • Ferredoxin-NADP Reductase / metabolism
  • Haptoglobins / analysis
  • Humans
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Methylenetetrahydrofolate Reductase (NADPH2) / metabolism
  • Polymorphism, Single Nucleotide / genetics*
  • Retrospective Studies
  • Sulfhydryl Compounds / blood
  • Vitiligo / blood
  • Vitiligo / genetics*


  • Haptoglobins
  • Sulfhydryl Compounds
  • Ceruloplasmin
  • methionine synthase reductase
  • Ferredoxin-NADP Reductase
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Cystathionine beta-Synthase