The Role of Folate Dependent Genetic Susceptibility in The Risk of Multiple Sclerosis

Background: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) of unknown cause. Epidemiological studies implicate that genetic and environmental factors interplay major roles in the etiology of MS. Several investigators have reported elevated plasma homocysteine and reduced folate and B vitamin levels in MS. Aberrations in one-carbon metabolism have impact in the pathophysiology by genetic susceptibility and increased the risk of MS. Furthermore, abnormalities in a carbon metabolism pathway may result from environmental factors such as reduced levels of vitamin B and folate due to inadequate B vitamin and folate intake from foods or the problems on their synthesis, and genetic factors such as polymorphism in folate – dependent enzymes.

Results: Many studies showed conflictive results genetic polymorphisms on the risk of MS. In the present review, we have emphasized the genetic susceptibility to the risk of MS, especially genetic polymorphisms on one carbon metabolism pathway. The associations on individual differences on the levels of homocysteine, B vitamin, folic acid due to genetic make-up and the risk of MS will be discussed. There are numerous reasons causing the development of MS especially, individual susceptibility should not be neglected. We have focused on three gene polymorphisms namely Methylene tetrahydrofolate reductase (MTHFR) C677T, A1298C and Methionine synthase (MTR) G66A since they are key enzymes on one carbon metabolism pathway.

Conclusion: So far conducted studies showed that genetic factors on products of one carbon pathway have major roles and these factors contribute to the development of MS. Individual differences in the development and treatment of the disease should not be overlooked.


Ali Erkan Asci and Bensu Karahalil

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