Thank you for the links PK
Canada Mark said...
Here is the statement for any interested:
ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing
Well, one could choose to go with their review, or one could choose to go with the 2011 more cautious approach
Aliment Pharmacol Ther. 2011 Nov;34(10):1173-84. doi: 10.1111/j.1365-2036.2011.04864.x. Epub 2011 Oct 3.
Meta-analysis: hyperhomocysteinaemia in inflammatory bowel diseases.
Oussalah A1, Guéant JL, Peyrin-Biroulet L.
The magnitude of association between homocysteine metabolism and inflammatory bowel diseases (IBD) remains unknown, whereas the association between hyperhomocysteinaemia and thrombosis remains controversial in IBD.
To conduct a systematic review and meta-analysis to examine these issues.
The literature search was conducted using MEDLINE database and international conference abstracts from January 1966 to April 2011 and included all studies that evaluated plasma homocysteine level in IBD.
Twenty-eight studies evaluated the plasma homocysteine level and/or hyperhomocysteinaemia risk in IBD patients. Five studies assessed the association of hyperhomocysteinaemia with thrombosis. The mean plasma homocysteine level was significantly higher in IBD patients when compared with controls (weighted mean difference (WMD)=3.75 μmol/L; 95% CI, 2.23-5.26 μmol/L; P<0.0001; reference ranges for plasma homocysteine level: 5-12 μmol/L). The mean plasma homocysteine level did not differ between ulcerative colitis (UC) and Crohn's disease (CD) (WMD=0.41 μmol/L; 95% CI, -2.45 to 3.06 μmol/L; P=0.76). The risk of hyperhomocysteinaemia was significantly higher in IBD patients when compared with controls [odds ratio (OR)=4.65; 95% CI, 3.04-7.09; P<0.0001]. The risk of hyperhomocysteinaemia was not higher among IBD patients who experienced thromboembolic complications (OR=1.97; 95% CI, 0.83-4.67; P=0.12). Plasma folate level was inversely correlated with IBD risk associated with MTHFR C677T polymorphism (P=0.006).
The risk of hyperhomocysteinaemia is significantly higher in IBD patients when compared with controls. The risk assessment of hyperhomocysteinaemia-related thrombosis in IBD requires further investigation. Deficient folate status is associated with a higher impact of MTHFR C677T polymorphism on IBD risk.
Meanwhile - back to B2 with a bit of MTHFR thrown in - although same people seem to have brought out a conflicting study later
Dutch study said...
Methylation of the promoter region of tumor suppressor genes is increasingly recognized to play a role in cancer development through silencing of gene transcription. We examined the associations between dietary folate intake, MTHFR C677T genotype, and promoter methylation of six tumor suppressor and DNA repair genes. Patients with colorectal adenoma (n = 149) and controls (n = 286) with folate intake in the upper or lower tertile with the CC or TT genotype were selected from a case-control study. Methylation-specific PCRs were conducted on colorectal adenoma specimens. The percentages of promoter methylation ranged from 15.7% to 64.2%. In case-case comparisons, folate was inversely associated with promoter methylation, especially among TT homozygotes. Case-control comparisons suggested that folate was not associated with the occurrence of adenomas with promoter methylation, and increased the risk of unmethylated adenomas, especially in TT homozygotes. The interactions between folate and MTHFR genotype were most pronounced for O6-MGMT: compared with CC homozygotes with low folate intake, the adjusted odds ratios (95% confidence interval) of having a methylated O6-MGMT promoter were 3.39 (0.82-13.93) for TT homozygotes with low folate intake and 0.37 (0.11-1.29) for TT homozygotes with high folate intake (P interaction = 0.02); the odds ratios for the occurrence of adenomas without methylation were 0.57 (0.16-2.11) for TT homozygotes with low folate intake and 3.37 (1.17-9.68) for TT homozygotes with high folate intake (P interaction = 0.03). In conclusion, folate intake seems to be inversely associated with promoter methylation in colorectal adenomas in case-case comparisons, and was positively associated with the occurrence of adenomas without promoter methylation in case-control comparisons, especially for TT homozygotes. (Cancer Epidemiol Biomarkers Prev 2007;16(2):327–33)
Yes over and over these studies supplement B12 and folate without B2 - yet B2 is known to be necessary to protect mucous membranes and it is known that B2 is taken up as a co-factor - so strange how it has been so little researched - and again, seems particularly relevant for those who are homoz c677t such as myself which is perhaps why it is ringing such bells.
Riboflavin and Methylenetetrahydrofolate Reductase
Steinar Hustad, Jern Schneede, and Per Magne Ueland.
The flavoenzyme methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, which serves as a methyl group donor in the conversion of homocysteine to methionine. In rats, experimental riboflavin deficiency is associated with low MTHFR activity and reduced levels of 5-methyltetrahydrofolate. In humans, reduced enzyme activity caused by the commonly occurring 677C→T substitution of the MTHFR gene is associated with elevated plasma homocysteine. The mutant enzyme has lower affinity for its flavin cofactor than the wild-type enzyme, and recent studies show that plasma homocysteine is inversely related to riboflavin in subjects with the T-allele. This indicates that the metabolic effect of the 677C→T polymorphism is related to riboflavin status, which may have implications for future studies on the relationship between this polymorphism and various clinical and biochemical endpoints.