9 research outputs found
Is MTHFR 677 C>T Polymorphism Clinically Important in Polycystic Ovarian Syndrome (PCOS)? A Case-Control Study, Meta-Analysis and Trial Sequential Analysis.
BACKGROUND:Optimum efficiency of the folate pathway is considered essential for adequate ovarian function. 677 C>T substitution in the 5, 10-methylene tertrahydrofolatereductase (MTHFR) gene compromises activity of the MTHFR enzyme by about 50%. The significance of correlation between 677C>T substitution and PCOS remains dubious due to the low power of published studies. METHODS AND RESULTS:We analyzed MTHFR 677 C>T site in ethnically two different PCOS case-control groups (total 261 cases and 256 controls) from India. The data analysis revealed a lack of association between this polymorphism and PCOS [OR = 1.11 (95%CI = 0.71-1.72), P = 0.66]. Group-wise analysis on the basis of ethnicity also revealed no association in any of the ethnic groups [Indo-Europeans, P = 1; Dravidians, P = 0.70]. Homocysteine levels did not differ significantly between cases (15.51 μmol/L, SD = 2.89) and controls (15.89 μmol/L, SD = 2.23). We also undertook a meta-analysis on 960 cases and 1028 controls, which suggested a significant association of the substitution with PCOS in the dominant model of analysis (OR = 1.47 (95%CI = 1.04-2.09), P = 0.032]. Trial sequential analysis corroborated findings of the traditional meta-analysis. However, we found that the conclusions of meta-analysis were strongly influenced by studies that deviated from the Hardy Weinberg equilibrium. A careful investigation of each study and a trial sequential analysis suggested that 677 C>T substitution holds no clinical significance in PCOS in most of the populations. CONCLUSION:In conclusion, MTHFR 677 C>T polymorphism does not affect PCOS risk in India. The association seen in the meta-analysis is due to an outlier study and studies showing deviation from the Hardy Weinberg equilibrium
Sensitivity analysis excluding the studies not fitting the Hardy Weinberg equilibrium.
<p>Sensitivity analysis excluding the studies not fitting the Hardy Weinberg equilibrium.</p
Meta-analysis.
<p>Forest plot showing the odds ratio, p value and direction of association between MTHFR 677 C>T polymorphism and PCOS. The Z value shows the degree and direction of the relationship, whereas the P value shows significance of the relationship. The horizontal bar shows the range of OR with a square in the centre, size of the latter is directly proportional to the weight given to each study. The direction of projection of the horizontal bar shows the direction of association.</p
Distribution and comparison of various clinical parameters between hyper- and normo-androgenic groups.
<p>Distribution and comparison of various clinical parameters between hyper- and normo-androgenic groups.</p
Results of meta-analysis (random effects model) using different analysis models.
<p>Results of meta-analysis (random effects model) using different analysis models.</p
Funnel plot of precision by log odds ratio showing the absence of publication bias.
<p>Funnel plot of precision by log odds ratio showing the absence of publication bias.</p
PRISMA flow diagram.
<p>The flow diagrams shows screening of literature and selection of studies for meta-analysis.</p