Association of elevated homocysteine levels and Methylenetetrahydrofolate reductase (MTHFR) 1298 A > C polymorphism with Vitiligo susceptibility in Gujarat

•Elevated plasma homocysteine and reduced vitamin B12 levels have been demonstrated in vitiligo patients.•MTHFR 1298A > C polymorphism was found to be associated with vitiligo.•MTHFR 1298A > C polymorphism was correlated with elevated homocysteine levels in vitiligo.•In-silico analysis implica...

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Published in:Journal of dermatological science 2018-05, Vol.90 (2), p.112-122
Main Authors: Jadeja, Shahnawaz D., Mansuri, Mohmmad Shoab, Singh, Mala, Patel, Hima, Marfatia, Yogesh S., Begum, Rasheedunnisa
Format: Article
Language:English
Subjects:
Adolescent
Adult
Case-Control Studies
Child
Computer Simulation
Female
Gene Frequency
Genetic polymorphisms
Genetic Predisposition to Disease
Genotype
Homocysteine
Homocysteine - blood
Humans
Hyperhomocysteinemia - blood
Hyperhomocysteinemia - epidemiology
Hyperhomocysteinemia - genetics
India - epidemiology
Male
Methylenetetrahydrofolate Reductase (NADPH2) - genetics
Middle Aged
MTHFR
Polymorphism, Restriction Fragment Length
Polymorphism, Single Nucleotide
Vitamin B 12 - blood
Vitamin B12
Vitiligo
Vitiligo - blood
Vitiligo - epidemiology
Vitiligo - genetics
Young Adult
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Summary:•Elevated plasma homocysteine and reduced vitamin B12 levels have been demonstrated in vitiligo patients.•MTHFR 1298A > C polymorphism was found to be associated with vitiligo.•MTHFR 1298A > C polymorphism was correlated with elevated homocysteine levels in vitiligo.•In-silico analysis implicated structural changes in MTHFR due to Ala222Val and Glu429Ala substitution. Several studies have reported hyperhomocysteinemia in vitiligo patients, suggesting the potential role of elevated homocysteine levels in precipitating vitiligo. We aimed to estimate homocysteine and vitamin B12 levels, and to investigate the role of MTHFR 677 C > T and 1298 A > C polymorphisms in vitiligo susceptibility in Gujarat population. Homocysteine and vitamin B12 levels were estimated in plasma of 55 vitiligo patients and 60 controls by Electrochemiluminescence immunoassay (ECLIA). Polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) and amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) techniques were used to genotype MTHFR 677 C > T and 1298 A > C polymorphisms in 520 vitiligo patients and 558 controls. Our results showed significantly elevated homocysteine levels (p = 0.0003) as well as significant decrease in vitamin B12 levels (p = 0.0102) in vitiligo patients, as compared to controls. No significant difference in genotype and allele frequencies of MTHFR 677 C > T polymorphism was observed among patients and controls, however, the frequency of ‘CC’ genotype of MTHFR 1298 A > Cpolymorphism was significantly increased in patients as compared to controls (p = 0.0151). Analysis based on the type of vitiligo revealed a significant increase in ‘C’ allele of MTHFR 1298 A > C polymorphism in patients with generalized (p = 0.003) and active (p = 0.007) vitiligo as compared to controls. Both the polymorphisms of MTHFR were in low linkage disequilibrium (LD) and susceptible ‘TC’ haplotype was more frequently observed (p = 0.008) in vitiligo patients. Interestingly, elevated homocysteine levels were also positively correlated with MTHFR 1298 A > C polymorphism in vitiligo patients. Structure based in silico prediction revealed structural perturbations in MTHFR protein due to Ala222Val and Glu429Ala amino acid substitution. The present findings suggest that MTHFR 1298 A > C polymorphism and, altered homocysteine and vitamin B12 levels might play a vital role in the precipitation of vitiligo.
ISSN:0923-1811
1873-569X
DOI:10.1016/j.jdermsci.2018.01.003