Genetic investigation of methylenetetrahydrofolate reductase (MTHFR) and catechol-O-methyl transferase (COMT) in multiple sclerosis

Tajouri, Lotfi; Martin, Virginie; Gasparini, Claudia Francesca; Ovcaric, Micky; Curtain, Rob; Lea, Rodney Arthur; Haupt, Larisa M.; Csurhes, Peter A.; Pender, Michael P.; Griffiths, Lyn R.

doi:10.1016/j.brainresbull.2006.01.005

Cited by 26 publications

(27 citation statements)

References 25 publications

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“…Accordingly, Tajouri et al (2006) C677T genotype of an Australian MS and unaffected populations and showed that mutant MTHFR genotype (T/T) was slightly, however not significantly, more presented in the MS group. Interestingly, in their study, the T/T was 1.5-fold more prevalent in MS patients compared to control group, which is very close to what we have observed in our study (1.7-fold increase).…”

Section: Discussionmentioning

confidence: 91%

Inflammatory Profile, Age of Onset, and the MTHFR Polymorphism in Patients with Multiple Sclerosis

et al. 2010

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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.

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Section: Discussionmentioning

confidence: 91%

Inflammatory Profile, Age of Onset, and the MTHFR Polymorphism in Patients with Multiple Sclerosis

et al. 2010

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“…On the contrary, horizontal agarose gels are easier to prepare and stain, non toxic and also allow large number of samples to be loaded on a single gel through the use of multiple adjacent combs. By eliminating the constant recognition sequence found in close proximity to the recognition sequence of interest, which is a novel approach, the ability of medium percentage agarose gels to resolve the informative bands within a short electrophoresis time was significantly increased, as the difference in length between the indicative fragments was increased from 18 bp, which is commonly found in the literature [21][22][23][24][25], to 36 bp, which is unprecedented. Therefore, the use of high concentration agarose gels (4-5%) which are costly and difficult to handle and prepare, can be avoided [28,29].…”

Section: Resultsmentioning

confidence: 73%

“…By eliminating the constant recognition sequence found in close proximity to the recognition sequence of interest, which is a novel approach, the ability of medium percentage agarose gels to resolve the informative bands within a short electrophoresis time was significantly increased, as the difference in length between the indicative fragments was increased from 18 bp, which is commonly found in the literature [21][22][23][24][25], to 36 bp, which is unprecedented. Therefore, the use of high concentration agarose gels (4-5%) which are costly and difficult to handle and prepare, can be avoided [28,29]. Furthermore, it was possible to reduce electrophoresis buffer concentration used down to 20% of that commonly used in order to allow the application of a high electric field strength (16 V/cm ) resulting in extremely short separation time (16 min) and distance (3cm) .…”

Section: Resultsmentioning

confidence: 73%

“…The restriction enzyme NlaIII has been used for Val158Met detection by PCR-RFLP [21][22][23][24][25]. However, the presence of NlaIII recognition sequences in close proximity to the SNP locus has limited many aspects of the use of PCR-RFLP in the detection.…”

Section: Resultsmentioning

confidence: 99%

“…PCR-RFLP (with NlaIII as the restriction enzyme) has been the most widely used method for the detection of Val158Met [21][22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

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Detection of catechol-O-methyltransferase (COMT) Val158Met Polymorphism by a New Optimized PCR-RFLP Method

Lajin¹,

Alachkar²

2011

Am. J. Biomed. Sci.

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The transition from G to A at nucleotide 21881 of the human catechol-O-methyltransferase (COMT) gene produces a functional genetic polymorphism (Val158Met) that has been shown to render an enzyme with reduced activity. A new highly optimized PCR-RFLP method for the detection of this polymorphism is described. The method utilizes the same restriction enzyme commonly used for PCR-RFLP detection of Val158Met, NlaIII. However, The SNP-containing fragment to be amplified was selected as to extremely simplify the restriction fragments pattern generated resulting in faster separation using 2.5% agarose gel electrophoresis. The presence of a Valine or Methionine allele is indicated by a 108 bp or 72 bp fragment, respectively. Electrophoresis conditions were optimized to decrease separation time and distance down to 16 min and 3 cm, respectively. The proposed method can serve as a fast, simple, and cost effective alternative to the PCR-RFLP methods commonly used for the detection of Val158Met, a polymorphism that is being thoroughly investigated in a broad range of biomedical fields.

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Regulation of redox forms of plasma thiols by albumin in multiple sclerosis after fasting and methionine loading test

et al. 2009

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Increases in plasma concentrations of total homocysteine (tHcy) have recently been reported in multiple sclerosis (MS) as the alteration of the methionine cycle for the onset of autoimmune diseases. Homocysteine (Hcy) and cysteine (Cys) are generated by the methionine cycle and transsulfuration reactions. Their plasma levels are subjected to complex redox changes by oxidation and thiol/disulfide (SH/SS) exchange reactions regulated by albumin. The methionine loading test (MLT) is a useful in vivo test to assay the functionality of the methionine cycle and transsulfuration reactions. Time courses of redox species of Cys, cysteinylglycine (CGly), Hcy, and glutathione have been investigated in plasma of MS patients versus healthy subjects after an overnight fasting, and 2, 4, and 6 h after an oral MLT (100 mg/kg body weight), to detect possible dysfunctions of the methionine cycle, transsulfuration reactions and alterations in plasma distribution of redox species. After fasting, the MS group showed a significant increase in cysteine-protein mixed disulfides (bCys) and total Cys (tCys). While plasma bCys and tCys in MS group remained elevated after methionine administration when compared to control, cystine (oxCys) increased significantly with respect to control. Although increased plasma concentrations of bCys and tCys at fasting might reflect an enhance of transsulfuration reactions in MS patients, this was not confirmed by the analysis of redox changes of thiols and total thiols after MLT. This study has also demonstrated that albumin-dependent SH/SS exchange reactions are a potent regulation system of thiol redox species in plasma.

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Genetic investigation of methylenetetrahydrofolate reductase (MTHFR) and catechol-O-methyl transferase (COMT) in multiple sclerosis

Cited by 26 publications

References 25 publications

Inflammatory Profile, Age of Onset, and the MTHFR Polymorphism in Patients with Multiple Sclerosis

Inflammatory Profile, Age of Onset, and the MTHFR Polymorphism in Patients with Multiple Sclerosis

Detection of catechol-O-methyltransferase (COMT) Val158Met Polymorphism by a New Optimized PCR-RFLP Method

Regulation of redox forms of plasma thiols by albumin in multiple sclerosis after fasting and methionine loading test

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