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Strong association of 677 C>T substitution in the MTHFR gene with male infertility--a study on an indian population and a meta-analysis.

Gupta N, Gupta S, Dama M, David A, Khanna G, Khanna A, Rajender S - PLoS ONE (2011)

Bottom Line: Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme of folate and methionine metabolism, making it crucial for DNA synthesis and methylation.Meta-analysis was performed using Comprehensive Meta-analysis software (Version 2).The overall summary estimate (OR) for allele and genotype meta-analysis were 1.304 (p = 0.000), 1.310 (p = 0.000), respectively, establishing significant association of 677C>T polymorphism with male infertility. 677C>T substitution associated strongly with male infertility in Indian population.

View Article: PubMed Central - PubMed

Affiliation: Division of Endocrinology, Central Drug Research Institute (Council of Scientific and Industrial Research), Lucknow, Uttar Pradesh, India.

ABSTRACT

Background: Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme of folate and methionine metabolism, making it crucial for DNA synthesis and methylation. The objective of this study was to analyze MTHFR gene 677C>T polymorphism in infertile male individuals from North India, followed by a meta-analysis on our data and published studies.

Methodology/principal findings: We undertook genotyping on a total of 837 individuals including well characterized infertile (N = 522) and confirmed fertile (N = 315) individuals. The SNP was typed by direct DNA sequencing. Chi square test was done for statistical analysis. Published studies were searched using appropriate keywords. Source of data collection for meta-analysis included 'Pubmed', 'Ovid' and 'Google Scholar'. Those studies analyzing 677C>T polymorphism in male infertility and presenting all relevant data were included in meta-analysis. The genotype data for infertile subjects and fertile controls was extracted from each study. Chi square test was done to obtain odds ratio (OR) and p-value. Meta-analysis was performed using Comprehensive Meta-analysis software (Version 2). The frequency of mutant (T) allele (p = 0.0025) and genotypes (CT+TT) (p = 0.0187) was significantly higher in infertile individuals in comparison to fertile controls in our case-control study. The overall summary estimate (OR) for allele and genotype meta-analysis were 1.304 (p = 0.000), 1.310 (p = 0.000), respectively, establishing significant association of 677C>T polymorphism with male infertility.

Conclusions/significance: 677C>T substitution associated strongly with male infertility in Indian population. Allele and genotype meta-analysis also supported its strong correlation with male infertility, thus establishing it as a risk factor.

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Related in: MedlinePlus

Forest plot.Meta-analysis using genotype frequency (a), cumulative genotype meta-analysis using fixed effect (b) and random effect models (c).
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pone-0022277-g004: Forest plot.Meta-analysis using genotype frequency (a), cumulative genotype meta-analysis using fixed effect (b) and random effect models (c).

Mentions: Similar to allele meta-analysis, pooled odds ratio for mutant genotypes (CT+TT) showed statistically significant association with infertility adopting both fixed (p = 0.000, OR = 1.310, 95% CI = 1.173-1.462) and random (p = 0.018, OR = 1.290, 95% CI = 1.044-1.595) effect models (Figure 4a). The fixed effect model cumulative analysis showed that addition of the study of Paracchini et al (2006) turned the overall association significant (p = 0.023) (Figure 4b). With introduction of another two studies, p value became highly significant (p = 0.00, significant at 99% level of confidence) and stayed significant thereafter (Figure 4b). However, with random effect model, the overall association turned significant only after inclusion of the study of Gava et al, 2011 (p = 0.041) and further introduction of our study supported the inference (p = 0.018) (Figure 4c).


Strong association of 677 C>T substitution in the MTHFR gene with male infertility--a study on an indian population and a meta-analysis.

Gupta N, Gupta S, Dama M, David A, Khanna G, Khanna A, Rajender S - PLoS ONE (2011)

Forest plot.Meta-analysis using genotype frequency (a), cumulative genotype meta-analysis using fixed effect (b) and random effect models (c).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3140509&req=5

pone-0022277-g004: Forest plot.Meta-analysis using genotype frequency (a), cumulative genotype meta-analysis using fixed effect (b) and random effect models (c).
Mentions: Similar to allele meta-analysis, pooled odds ratio for mutant genotypes (CT+TT) showed statistically significant association with infertility adopting both fixed (p = 0.000, OR = 1.310, 95% CI = 1.173-1.462) and random (p = 0.018, OR = 1.290, 95% CI = 1.044-1.595) effect models (Figure 4a). The fixed effect model cumulative analysis showed that addition of the study of Paracchini et al (2006) turned the overall association significant (p = 0.023) (Figure 4b). With introduction of another two studies, p value became highly significant (p = 0.00, significant at 99% level of confidence) and stayed significant thereafter (Figure 4b). However, with random effect model, the overall association turned significant only after inclusion of the study of Gava et al, 2011 (p = 0.041) and further introduction of our study supported the inference (p = 0.018) (Figure 4c).

Bottom Line: Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme of folate and methionine metabolism, making it crucial for DNA synthesis and methylation.Meta-analysis was performed using Comprehensive Meta-analysis software (Version 2).The overall summary estimate (OR) for allele and genotype meta-analysis were 1.304 (p = 0.000), 1.310 (p = 0.000), respectively, establishing significant association of 677C>T polymorphism with male infertility. 677C>T substitution associated strongly with male infertility in Indian population.

View Article: PubMed Central - PubMed

Affiliation: Division of Endocrinology, Central Drug Research Institute (Council of Scientific and Industrial Research), Lucknow, Uttar Pradesh, India.

ABSTRACT

Background: Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme of folate and methionine metabolism, making it crucial for DNA synthesis and methylation. The objective of this study was to analyze MTHFR gene 677C>T polymorphism in infertile male individuals from North India, followed by a meta-analysis on our data and published studies.

Methodology/principal findings: We undertook genotyping on a total of 837 individuals including well characterized infertile (N = 522) and confirmed fertile (N = 315) individuals. The SNP was typed by direct DNA sequencing. Chi square test was done for statistical analysis. Published studies were searched using appropriate keywords. Source of data collection for meta-analysis included 'Pubmed', 'Ovid' and 'Google Scholar'. Those studies analyzing 677C>T polymorphism in male infertility and presenting all relevant data were included in meta-analysis. The genotype data for infertile subjects and fertile controls was extracted from each study. Chi square test was done to obtain odds ratio (OR) and p-value. Meta-analysis was performed using Comprehensive Meta-analysis software (Version 2). The frequency of mutant (T) allele (p = 0.0025) and genotypes (CT+TT) (p = 0.0187) was significantly higher in infertile individuals in comparison to fertile controls in our case-control study. The overall summary estimate (OR) for allele and genotype meta-analysis were 1.304 (p = 0.000), 1.310 (p = 0.000), respectively, establishing significant association of 677C>T polymorphism with male infertility.

Conclusions/significance: 677C>T substitution associated strongly with male infertility in Indian population. Allele and genotype meta-analysis also supported its strong correlation with male infertility, thus establishing it as a risk factor.

Show MeSH
Related in: MedlinePlus