title: Inflammatory profile, age of onset, and the MTHFR polymorphism in patients with multiple sclerosis.
abstract: Both genetic and inflammatory factors are suspected in the etiology of multiple sclerosis (MS). Of genetic factors, the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism has been associated with increased levels of plasma homocysteine, a neuronal excitotoxic amino acid. Sclerotic patients also have elevated levels of plasma and CSF homocysteine. In this study, the association between C677T polymorphism and MS was tested by recruiting 230 healthy and 194 multiple sclerotic age- and gender-matched patients. The MTHFR C677T polymorphism and the serum levels of inflammatory mediators IL-1β, TNFα, and CRP were measured. TNFα, CRP, and IL-1β levels were significantly higher in sclerotic patients. T allele was 1.7 times more present in this group. In patient's group, the levels of all inflammatory mediators were higher in T/T compared to two other genotypes. Evaluation of the age of onset of disease revealed that subjects with T allele developed the MS disease, almost 4 years sooner than other genotype. We concluded that having T allele of C677T in MS might be accompanied with higher levels of serum inflammatory mediators and a vulnerability to earlier age of onset of disease. Further studies are needed to elucidate the underlying mechanisms.
authors.affiliation: Endocrinology and Metabolism Research Center, Tehran University of Medical Sciences, North Kargar Ave., 5th Floor, Dr. Shariati Hospital, Tehran 14114, Iran.
authors.forename: Sudabeh
authors.initials: S
authors.lastname: Alatab
authors.forename: Arash
authors.initials: A
authors.lastname: Hossein-nezhad
authors.forename: Khadijeh
authors.initials: K
authors.lastname: Mirzaei
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Mokhtari
authors.forename: Gholamreza
authors.initials: G
authors.lastname: Shariati
authors.forename: Azam
authors.initials: A
authors.lastname: Najmafshar
mesh_terms: D000328:Adult; D017668:Age of Onset; D016022:Case-Control Studies; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000276:immunology*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000201:enzymology / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology; D011110:Polymorphism, Genetic; D055815:Young Adult
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)