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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...

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Autores principales: Carlus, S. Justin, Sarkar, Saumya, Bansal, Sandeep Kumar, Singh, Vertika, Singh, Kiran, Jha, Rajesh Kumar, Sadasivam, Nirmala, Sadasivam, Sri Revathy, Gireesha, P. S., Thangaraj, Kumarasamy, Rajender, Singh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4794143/
https://www.ncbi.nlm.nih.gov/pubmed/26983014
http://dx.doi.org/10.1371/journal.pone.0151510
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author Carlus, S. Justin
Sarkar, Saumya
Bansal, Sandeep Kumar
Singh, Vertika
Singh, Kiran
Jha, Rajesh Kumar
Sadasivam, Nirmala
Sadasivam, Sri Revathy
Gireesha, P. S.
Thangaraj, Kumarasamy
Rajender, Singh
author_facet Carlus, S. Justin
Sarkar, Saumya
Bansal, Sandeep Kumar
Singh, Vertika
Singh, Kiran
Jha, Rajesh Kumar
Sadasivam, Nirmala
Sadasivam, Sri Revathy
Gireesha, P. S.
Thangaraj, Kumarasamy
Rajender, Singh
author_sort Carlus, S. Justin
collection PubMed
description 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.
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spelling pubmed-47941432016-03-23 Is MTHFR 677 C>T Polymorphism Clinically Important in Polycystic Ovarian Syndrome (PCOS)? A Case-Control Study, Meta-Analysis and Trial Sequential Analysis Carlus, S. Justin Sarkar, Saumya Bansal, Sandeep Kumar Singh, Vertika Singh, Kiran Jha, Rajesh Kumar Sadasivam, Nirmala Sadasivam, Sri Revathy Gireesha, P. S. Thangaraj, Kumarasamy Rajender, Singh PLoS One Research Article 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. Public Library of Science 2016-03-16 /pmc/articles/PMC4794143/ /pubmed/26983014 http://dx.doi.org/10.1371/journal.pone.0151510 Text en © 2016 Carlus et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Carlus, S. Justin
Sarkar, Saumya
Bansal, Sandeep Kumar
Singh, Vertika
Singh, Kiran
Jha, Rajesh Kumar
Sadasivam, Nirmala
Sadasivam, Sri Revathy
Gireesha, P. S.
Thangaraj, Kumarasamy
Rajender, Singh
Is MTHFR 677 C>T Polymorphism Clinically Important in Polycystic Ovarian Syndrome (PCOS)? A Case-Control Study, Meta-Analysis and Trial Sequential Analysis
title Is MTHFR 677 C>T Polymorphism Clinically Important in Polycystic Ovarian Syndrome (PCOS)? A Case-Control Study, Meta-Analysis and Trial Sequential Analysis
title_full Is MTHFR 677 C>T Polymorphism Clinically Important in Polycystic Ovarian Syndrome (PCOS)? A Case-Control Study, Meta-Analysis and Trial Sequential Analysis
title_fullStr Is MTHFR 677 C>T Polymorphism Clinically Important in Polycystic Ovarian Syndrome (PCOS)? A Case-Control Study, Meta-Analysis and Trial Sequential Analysis
title_full_unstemmed Is MTHFR 677 C>T Polymorphism Clinically Important in Polycystic Ovarian Syndrome (PCOS)? A Case-Control Study, Meta-Analysis and Trial Sequential Analysis
title_short Is MTHFR 677 C>T Polymorphism Clinically Important in Polycystic Ovarian Syndrome (PCOS)? A Case-Control Study, Meta-Analysis and Trial Sequential Analysis
title_sort is mthfr 677 c>t polymorphism clinically important in polycystic ovarian syndrome (pcos)? a case-control study, meta-analysis and trial sequential analysis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4794143/
https://www.ncbi.nlm.nih.gov/pubmed/26983014
http://dx.doi.org/10.1371/journal.pone.0151510
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