Association Between MTHFR Genetic Variants and Multiple Sclerosis in a Southern Iranian Population

Multiple sclerosis (MS) is a demyelinating neuro- inflammatory autoimmune disease of the central nervous
system. Genetic predisposition has long been suspected in the etiology of this disease. The association between
MTHFR polymorphisms and MS has been ivestigated in different ethnic groups. We investigated the association
between MTHFR C677T and A1298C missense variants and MS in 180 patients and 231 age- and gender-
matched healthy controls in a Southern Iranian population. The mutagenically separated PCR (MS-PCR) and
PCR-RFLP methods were used to genotype MTHFR at position 677 and 1298, respectively. Compared with
controls, we observed a strong association between two MTHFR variants and the risk of developing MS.
Subjects carrying 677T allele (CT and TT genotypes) had increased susceptibility to MS as compared to those
carrying CC genotype (odds ratio (OR) for CT= 2.9, 95% confidence interval (95% CI)= 1.88-4.49; OR for TT=
6.23, 95% CI= 3.08-12.59). The variant 1298AC genotype also increased the risk for MS among our study
population (OR= 2.14, 95% CI= 1.37-3.34). Combined genotype analysis for two MTHFR SNPs revealed that
compared to the wild type genotypes (677CC/1298AA), 3 genotypes including TT/AC, CT/AC, and TT/AA were
significantly at increased risk for MS development (OR= 13.9, 5.3, and 4.9, respectively). Our results suggest a
possible gene dose- dependent association between MTHFR mutrant alleles and the risk of MS development.