Is the CAG repeat of mitochondrial DNA polymerase gamma (POLG) associated with male infertility? A multi-centre French study

Aknin‐Seifer, Isabelle; Touraine, Renaud; Lejeune, Hervé; Jimenez, Clément; Chouteau, J.; Siffroi, Jean Pierre; McElreavey, Ken; Bienvenu, Thierry; Patrat, Catherine; Lévy, Rachel

doi:10.1093/humrep/deh666

Cited by 49 publications

(29 citation statements)

References 13 publications

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“…Rovio et al 1999 [5], have shown the frequent (88 %) occurrence of genotype 10/10 in different ethnic group. As found by Krausz et al 2004; Aknin-Seifer et al 2005 [11,12], this study also suggested that the CAG repeat of the POLG gene does not play a significant role in men with severe male factor infertility.…”

Section: Resultssupporting

confidence: 76%

“…Expansion of CAG repeat in some genes is associated with various human pathologies. Implication of POLG CAG repeats in infertility is suggested by copious studies [6][7][8][9][10], but are debated [11][12][13][14][15]. As it is not clear whether the variable CAG genotype is one of the contributing factor for male infertility, an attempt was made to screen the CAG repeat motif of POLG gene exclusively in infertile men from two different districts of Tamil Nadu, South India.…”

Section: Introductionmentioning

confidence: 99%

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Mitochondrial DNA polymerase gamma gene polymorphism is not associated with male infertility

Poongothai

2013

J Assist Reprod Genet

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Purpose CAG repeat length of human miotochondrial DNA Polymerase gamma (POLG) gene is polymorphic with a major allele at 10 repeats and considered as the common allele whereas the mutant alleles (not 10/not 10 CAG repeats) were found to be associated with oligospermia / oligoasthenospermia in male infertility. To explore whether CAG trinucleotide repeat expansion in exon 1 of POLG gene is associated with spermatogenic failure. Methods One hundred twenty four infertile men (sperm count <20 million/ml) and 60 normozoospermic (sperm count >20 million/ml) control Indian men of Tamil Nadu, were enrolled. DNA was extracted from 10 ml of peripheral blood and from semen using standard procedures. CAG repeat expansion was analyzed by polymerase chain reaction. Amplified products were quantified by 2 % agarose gel electrophoresis and subjected to genescan analysis to ascertain the size of POLG-CAG alleles. Results This analysis interestingly revealed that the common allele 10 (10-CAG repeats) was widespread in infertile and normozoospermic control men with a frequency of 79 % and 71.7 % respectively. No statistical significance was found in POLG genotypic frequency distribution between infertile men and normospermic men. Conclusion The present study confirmed no association between the POLG gene polymorphism and male infertility. Thus, if associated with infertility, the POLG gene polymorphism should be only considered as a minor possible contributing factor in infertile male patients with no impact on obtaining a pregnancy.

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Section: Resultssupporting

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Mitochondrial DNA polymerase gamma gene polymorphism is not associated with male infertility

Poongothai

2013

J Assist Reprod Genet

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“…Some studies combined three (azoospermia, oligozoospermia and asthenozoospermia) or more subgroups of idiopathic male infertility to examine the distribution of CAG-repeat variants of the POLG gene. 12,13,15,[17][18][19] On the contrary, some studies analyzed only one subgroup or excluded some subgroups, such as Rani et al, 16 who studied only the association between the CAG-repeat variant and POLG-CAG-repeat variant and male infertility SY Liu et aloligoasthenozoospermia; Rovio et al, 9 who excluded azoospermic and severely oligozoospermic men; and this study, which only included asthenozoospermic and oligoasthenozoospermic men. All studies excluded patients with genetic causes of infertility (karyotype mutations, Kallman syndrome, Y-chromosome microdeletions and cystic fibrosis mutations) from the analysis; however, not all known genetic causes of male infertility were reported to be excluded in all studies.…”

Section: Polg-cag-repeat Variant and Male Infertility Sy Liu Et Al 302mentioning

confidence: 86%

“…The results from this study and other casecontrol studies 9,[11][12][13][15][16][17][18][19] were combined for meta-analysis. The departure from HWE for the control group in each study was assessed using a Pearson x 2 test for goodness of fit in the HWE program (http:// ihg2.helmholtz-muenchen.de/cgi-bin/hw/hwa1.pl).…”

Section: Statistical Analysis and Meta-analysismentioning

confidence: 99%

“…10 More and more evidence has indicated that the length of the CAG-repeat may influence the function of spermatozoa, and several studies have confirmed that an alteration in the length of the CAG-repeat is associated with male infertility; 9,11,12 however, some studies have failed to establish such an association. [13][14][15][16][17][18][19] Because there are different distributions of the CAG-repeat length among healthy individuals from different ethnic groups, 10,14,16 a determination of the distribution of CAG-repeat length is necessary before an association study between male infertility and CAG-repeat variants in the POLG gene can be carried out.…”

Section: Introductionmentioning

confidence: 99%

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CAG-repeat variant in the polymerase γ gene and male infertility in the Chinese population: a meta-analysis

Liu¹,

Zhang²,

Haiying³

et al. 2010

Asian J Androl

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Several studies have reported a relationship between the length of the CAG-repeat in the polymerase c (POLG) gene and male infertility. However, other studies have not reproduced this result. In our study, the POLG-CAG-repeat length was analyzed in 535 healthy individuals from six Chinese Han populations living in different provinces. The frequencies of 10-CAG alleles and genotypes were high (97.38 and 94.13%, respectively), with no significant difference among the six Chinese Han populations. Furthermore, we determined the distribution of the POLG-CAG-repeat in 150 infertile men and 126 fertile men. Our study suggested that the distributions of POLG-CAG-repeat alleles and genotypes were not significantly different between infertile (95.67 and 92.67%, respectively) and fertile men (97.22 and 94.44%, respectively). In a subsequent meta-analysis, combining our data with data from previous studies, a comparison of the CAG-repeat alleles in fertile versus infertile men showed no obvious risk for male infertility associated with any particular allele (pooled odds ratio (OR)50.94; 95% confidence interval (CI): 0.60-1.48). The significance level was not attained with any of the following genetic models: homozygote comparison (not 10/not 10 versus 10/10: OR51.34; 95% CI: 0.66-2.72), heterozygote comparison (10/not 10 versus 10/10: OR51.04; 95% CI: 0.78-1.38), dominant model comparison (not 10/not 10110/ not 10 versus 10/10: OR51.08; 95% CI: 0.79-1.47) and recessive genetic comparison (not 10/not 10 versus 10/not 10110/10: OR51.31; 95% CI: 0.68-2.55). In conclusion, there is no significant difference of the frequencies of POLG-CAG-repeat variants among six Chinese Han populations, and this polymorphism may not be associated with Chinese male infertility. On the basis of a meta-analysis, there is no obvious association between CAG-repeat variants of the POLG gene and male infertility.

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Molecular Genetics of Spermatogenic Disturbances

Krausz¹

2009

Encyclopedia of Life Sciences

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A large proportion of male infertility is predicted to be related to genetic factors. These factors may act directly at the testicular level or through the endocrine regulation of the testis. A number of new causative mutations have been identified in hypogonadotrophic hypogonadism allowing a genetic diagnosis in approximately 30–40% of cases. However, search for causative mutations in Y‐chromosome, autosomal and X‐linked genes with predicted spermatogenic function have been substantially unsuccessful with some rare exceptions. Up to now, only Y‐chromosome rearrangements such as AZoospermia Factor ( AZF ) deletions and gr/gr deletion have been confirmed as molecular genetic causes of primitive testicular failure. Key concepts: Spermatogenic failure can be caused by genetic factors acting at the pre‐testicular or directly at the testicular level. Mutation in genes involved in the hormonal regulation of the testis (pre‐testicular level) is associated with hypogonadotrophic hypogonadism. Genetic factors involved in primitive testicular failure can be divided in chromosomal abnormalities and monogenic mutations. Microdeletions in specific regions of the long arm of the Y‐chromosome ( AZF regions) represent the most frequent molecular genetic cause of primitive testicular failure. The diagnosis of AZF deletions is clinically relevant since it provides the aethiology of infertility, has a prognostic value for testicular sperm retrieval and the deletion will be obligatory transmitted to the male offspring. gr/gr deletion of the AZFc region is the only significant risk factor for impaired sperm production identified to date. Search for X‐linked and autosomal gene mutations/polymorphisms has been largely unsuccessful. Given the polygenic nature of male infertility a major advancement will likely be achieved from future studies based on whole genome analyses in large study populations.

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Is the CAG repeat of mitochondrial DNA polymerase gamma (POLG) associated with male infertility? A multi-centre French study

Abstract: Under our conditions, our study does not confirm any relationship between the polymorphic CAG repeat in the POLG gene and male infertility.

Cited by 49 publications

References 13 publications

Mitochondrial DNA polymerase gamma gene polymorphism is not associated with male infertility

Mitochondrial DNA polymerase gamma gene polymorphism is not associated with male infertility

CAG-repeat variant in the polymerase γ gene and male infertility in the Chinese population: a meta-analysis

Molecular Genetics of Spermatogenic Disturbances

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