Influence of Methylenetetrahydrofolate Reductase <i>C677T</i> Gene Polymorphisms in Algerian Infertile Men with Azoospermia or Severe Oligozoospermia

Djalila, Chellat; Rezgoune, Mohamed Larbi; Hamane, Douadi; Semmame, Ouarda; Benlatreche, C.; Abadi, N.; Satta, Dalila

doi:10.1089/gtmb.2011.0367

Cited by 16 publications

(9 citation statements)

References 29 publications

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“…Previous epidemiological studies have suggested ethnicity as a factor, where only certain ethnic populations revealed an association between this SNP and male infertility (Gupta et al, 2011;Chellat et al, 2012;Naqvi et al, 2014;Gong et al, 2015). The men in this study, however, were not evaluated for ethnicity.…”

Section: Discussionmentioning

confidence: 80%

Evaluation of DNA methylation at imprinted DMRs in the spermatozoa of oligozoospermic men in association withMTHFRC677T genotype

Louie

Minor

et al. 2016

Andrology

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SUMMARYAltered DNA methylation has been previously identified in the spermatozoa of infertile men; however, the origins of these errors are poorly understood. DNA methylation is an epigenetic modification which is thought to play a fundamental role in male germline development. DNA methylation reactions rely on the cellular availability of methyl donors, which are primarily products of folate metabolism, where a key enzyme is methylenetetrahydrofolate reductase (MTHFR). The MTHFR C677T single nucleotide polymorphism (SNP) reduces enzyme activity and may potentially alter DNA methylation processes during germline development. The objective of this study was to determine whether altered DNA methylation in spermatozoa is associated with the MTHFR C677T SNP. DNA methylation was evaluated at the H19, IG-GTL2, and MEST imprinted differentially methylated regions in the spermatozoa of 53 men -44 oligozoospermic men and nine fertile men with normal sperm parameters via bisulfite sequencing of sperm clones. The 44 infertile men were stratified by severity of oligozoospermia -three normal (>15 million spermatozoa/mL), eight moderate (5-15 million spermatozoa/mL), 23 severe (1-5 million spermatozoa/mL), and 10 very severe (<1 million spermatozoa/mL). MTHFR C677T SNP genotyping was conducted in a subset of 44 peripheral blood samples via restriction fragment length polymorphism. A total of three men -severe oligozoospermic and CT genotype -were found to be altered, which is defined as having ≥50% of their clones altered, where an altered clone was in turn defined as ≥50% of CpGs with incorrect DNA methylation patterns. The incidence of three altered men within the CT subgroup, however, was not significantly higher than the incidence in the CC subgroup. Taken together, altered DNA methylation in spermatozoa was not significantly associated with the MTHFR C677T SNP; however, there was a trend for higher incidence of alterations among severe oligozoospermic infertile men with CT genotypes.

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Section: Discussionmentioning

confidence: 80%

Evaluation of DNA methylation at imprinted DMRs in the spermatozoa of oligozoospermic men in association withMTHFRC677T genotype

Louie

Minor

et al. 2016

Andrology

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“…The impact of MTHFR gene SNPs on infertility risk has been studied in various ethnic groups [2], [13], [22]–[25], [27], [29], [37]–[43]. Most commonly studied MTHFR SNP, c.677C>T, has been established as a risk factor for male infertility in some populations [21–23, 37 and 39–41], but not in others [13], [24]–[25], [38], [42]–[43].…”

Section: Discussionmentioning

confidence: 99%

“…Most commonly studied MTHFR SNP, c.677C>T, has been established as a risk factor for male infertility in some populations [21–23, 37 and 39–41], but not in others [13], [24]–[25], [38], [42]–[43]. c.677C>T has been suggested to infertility risk by two meta-analyses [3 and 21], but denied doing so by a recent meta-analysis [44].…”

Section: Discussionmentioning

confidence: 99%

Significant Impact of the MTHFR Polymorphisms and Haplotypes on Male Infertility Risk

et al. 2013

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BackgroundMethylenetetrahydrofolate reductase (MTHFR) converts 5,10-methylene tetrahydrofolate to 5-methyl tetrahydrofolate and affects the activity of cellular cycles participating in nucleotide synthesis, DNA repair, genome stability, maintenance of methyl pool, and gene regulation. Genetically compromised MTHFR activity has been suggested to affect male fertility. The objective of the present study was to find the impact on infertility risk of c.203G>A, c.1298A>C, and c.1793G>A polymorphisms in the MTHFR gene.MethodsPCR-RFLP and DNA sequencing were used to genotype the common SNPs in the MTHFR gene in 630 infertile and 250 fertile males. Chi-square test was applied for statistical comparison of genotype data. Linkage disequilibrium between the SNPs and the frequency of common haplotypes were assessed using Haploview software. Biochemical levels of total homocysteine (tHcy) and folic acid were measured. Meta-analysis on c.1298A>C polymorphism was performed using data from ten studies, comprising 2734 cases and 2737 controls.Resultsc.203G>A and c.1298A>C were found to be unrelated to infertility risk. c.1793G>A was protective against infertility (P = 0.0008). c.677C>T and c.1793G>A were in significant LD (D’ = 0.9). Folic acid and tHcy level did not correlate with male infertility. Pooled estimate on c.1298A>C data from all published studies including our data showed no association of this polymorphism with male infertility (Odds ratio = 1.035, P = 0.56), azoospermia (Odds ratio = 0.97, P = 0.74), or oligoasthenoteratozoospermia (Odds ratio = 0.92, p = 0.29). Eight haplotypes with more than 1% frequency were detected, of which CCGA was protective against infertility (p = 0.02), but the significance of the latter was not seen after applying Bonferroni correction.ConclusionAmong MTHFR polymorphisms, c.203G>A and c.1298A>C do not affect infertility risk and c.1793G>A is protective against infertility. Haplotype analysis suggested that risk factors on the MTHFR locus do not extend too long on the DNA string.

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“…Results of these studies are contradictory. The MTHFR c.677TT genotype has been reported to be a candidate genetic risk factor for infertility in male patients in the studies performed in Germany, South Korea, Chine, Brasil, Iran and North India (Bezold et al ., ; Park et al ., ; Zhou‐Cun et al ., ; Gava et al ., ; Safarinejad et al ., ; Naqvi et al ., ), whereas the other studies from Netherlands, Italy, Algeria, Morocco‐ North Africa and South India did not find an association (Ebisch et al ., ; Stuppia et al ., ; Chellat et al ., ; Eloualid et al ., ; Vani et al ., ). In a meta‐analysis focusing on the relationship between the MTHFR c.677C>T polymorphism and male infertility, Wu et al .…”

Section: Discussionmentioning

confidence: 98%

The relationship between methylenetetrahydrofolate reductase c.677TT genotype and oligozoospermia in infertile male patients living in the Trakya region of Turkey

et al. 2014

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Methylenetetrahydrofolate reductase (MTHFR), the key enzyme of the folate metabolic pathway, has been reported to be five times more active in the testicles compared to other organs in adult mice. The aim of this study was to investigate the relationship between MTHFR c.677C>T and c.1298A>C polymorphisms and infertility in nonobstructive azoospermic and oligozoospermic male patients living in the Trakya region of Turkey. The study population included 75 nonobstructive azoospermic and 62 oligozoospermic, nonconsanguineous patients who were referred to the Department of Medical Genetics of Trakya University between 01.03.2012 and 01.06.2013 due to infertility and who had been diagnosed based on clinical examinations and spermiograms. All of the patients had a normal karyotype without a Y chromosome microdeletion. Melting curve analysis with labelled probes and primers that were designed by the manufacturers and the real-time polymerase chain reaction method were used. The MTHFR c.677TT genotype frequency in the oligozoospermic infertile male patient group was greater than that of the fertile control group [odds ratio (OR) = 2.675 (95% CI: 0.979-7.305), (P < 0.048)]. The MTHFR c.677TT genotype may be a genetic risk factor for oligozoospermic infertile male patients who live in the Trakya region of Turkey.

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Influence of Methylenetetrahydrofolate Reductase C677T Gene Polymorphisms in Algerian Infertile Men with Azoospermia or Severe Oligozoospermia

Abstract: The data suggest that the C677T MTHFR polymorphism is not a risk factor for idiopathic male subfertility in an Algerian population.

Cited by 16 publications

References 29 publications

Evaluation of DNA methylation at imprinted DMRs in the spermatozoa of oligozoospermic men in association withMTHFRC677T genotype

Evaluation of DNA methylation at imprinted DMRs in the spermatozoa of oligozoospermic men in association withMTHFRC677T genotype

Significant Impact of the MTHFR Polymorphisms and Haplotypes on Male Infertility Risk

The relationship between methylenetetrahydrofolate reductase c.677TT genotype and oligozoospermia in infertile male patients living in the Trakya region of Turkey

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