Methylenetetrahydrofolate Reductase (MTHFR) C677T Polymorphism and Subacute Combined Degeneration: Revealing a Genetic Predisposition.

Xin Zhang,Rui Li,Yue Liu,Chen Hou,Peng Tang,Li Chen,Peng Liu

doi:10.3389/fneur.2018.01162

Xin Zhang, Rui Li + Show 5 more

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https://doi.org/10.3389/fneur.2018.01162

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Abstract

Vitamin B12 deficiency is regarded as the prevailing cause of subacute combined degeneration of the spinal cord (SCD). Nevertheless, the genetic predisposition to SCD remains unclear. The aim of this study was to explore the association between methylenetetrahydrofolate reductase gene (MTHFR) C677T polymorphism and SCD. We investigated MTHFR C677T polymorphism in SCD patients and found that the distribution of MTHFR C677T genotypes was significantly different between SCD patients and age-matched controls. Furthermore, the T allele frequency was markedly increased in SCD compared with the controls. In addition, the plasma homocysteine concentrations in subjects with the TT genotype were significantly elevated compared to those with the CC genotype. Logistic regression analysis results revealed that the MTHFR C677T genotype (TT vs. CT and CC) and vitamin B12 deficiency were risk factors for SCD. Our findings indicate that the T allele of the MTHFR C677T confers a strong genetic predisposition to SCD and provide evidence of an association between MTHFR C677T polymorphism and SCD. These data reveal a potential mechanism underlying SCD.

Highlights

Subacute combined degeneration of the spinal cord (SCD) is pathologically characterized by demyelination and degeneration that occurs predominantly in the posterior and lateral columns of the spinal cord and, in rare cases, demyelination of peripheral nerves and white matter in the brain [1, 2]
The plasma homocysteine concentration is presented as a median. aA plasma vitamin B12 concentration < 180 pg/mL was defined as B12 deficiency. bA plasma folate concentration < 3.1 ng/mL was defined as folate deficiency
The results showed that both methylenetetrahydrofolate reductase gene (MTHFR) C677T genotype (TT vs. CT and CC) and vitamin B12 deficiency were positively correlated with SCD (OR = 2.882, 95% confidence intervals (95% CIs) 1.189 to 6.986, P = 0.019 and odds ratios (ORs) = 2.742, 95% CI 1.129 to 6.662, P = 0.026, respectively)

Summary

Introduction

Subacute combined degeneration of the spinal cord (SCD) is pathologically characterized by demyelination and degeneration that occurs predominantly in the posterior and lateral columns of the spinal cord and, in rare cases, demyelination of peripheral nerves and white matter in the brain [1, 2]. Vitamin B12 deficiency, which is believed to be associated with inadequate dietary intake and gastritis-associated vitamin B12 malabsorption, has long been regarded as the underlying cause of SCD [3, 4]. Methylation is required for the synthesis of myelin in the spinal cord [5]. Hypomethylation due to B12 deficiency is hypothesized to inhibit the conversion of homocysteine to methionine and to S-adenosyl methionine (SAM), affecting myelin synthesis. Elevated homocysteine levels are thought to lead to increased concentrations of S-adenosyl homocysteine

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