Why did MTHFR polymorphism studies show no increase in risk of CVD?
No or borderline significant relation has been found between the C677T MTHFR polymorphism and CVD; this has been thought to be a contention for disproving the hypothesis. However, careful statistical evaluation indicated that the studies addressing correlation between MTHFR polymorphism and CVD risk were inadequately powered due to smaller sample size, and the results are FALSE NEGATIVE. It has been found that the total homocysteine concentration was 2.6 mol/L higher in those with the TT than in those with the CC genotype. [12] With use of data from prospective studies, a 5-mol/L total homocysteine increment can be shown to be associated with an OR of 1.20-1.30. For a difference of 2.6 mol/L, this OR translates to 1.10-1.15. Standard sample size calculations show that to detect a relative risk in the range of 1.10-1.15 with a power of 80% and a significance level of 5%, 7,800-16,300 cases and an equal number of controls are required. This exceeds the sample size in the studies showing
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