Molecular analysis of polymerase gamma gene and mitochondrial polymorphism in fertile and subfertile men

Harris, T. P., Gomas, K. P., Weir, F., Holyoake, A. J., McHugh, P., Wu, M., Sin, Y., Sin, I. L. and Sin, F. Y. T. (2006) Molecular analysis of polymerase gamma gene and mitochondrial polymorphism in fertile and subfertile men. International Journal of Andrology, 29(3), pp. 421-433. (doi: 10.1111/j.1365-2605.2005.00633.x) (PMID:16487403)

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Abstract

CAG trinucleotide repeat length in the nuclear polymerase gamma gene (POLgamma) has been shown to be associated with men with reduced fertility. The present study investigated the frequency of CAG repeat length genotypes and three exonuclease motifs of the POLgamma in relation to the frequency of mitochondrial nucleotide substitutions. DNA from semen samples of 93 normozoospermic men and 192 non-normozoospermic men was isolated and the specific regions of the genes were amplified by polymerase chain reactions (PCR) and sequenced to identify mutations. The genotypic frequencies of pooled POLgamma CAG repeat lengths, =10/ not equal 10 heterozygotes and not equal 10/ not equal 10 homozygotes, were significantly different between normozoospermic and non-normozoospermic men (p < 0.05), with non-normozoospermic men having a slightly higher frequency of the =10/=10 genotypes. The allelic frequency for =10 is 0.79 and not equal10 is 0.21 for normozoospermic men and 0.85 and 0.15, respectively, for non-normozoospermic men (p < 0.025). There was no mutation detected in the exonuclease motifs in all the samples tested. Eighty normozoospermic and 124 non-normozoospermic semen samples were analysed for nucleotide substitutions in mitochondrial genes by PCR and sequencing. Heteroplasmic mutations were found in one azoospermic man, four asthenozoospermic men and two normozoospermic men. Only one asthenozoospermic man was heterozygous for the POLgamma genotype. Of the 17 men with non-synonymous nucleotide substitutions, 14 were homozygous for the POLgamma genotype. Non-normozoospermic men had twice as many nucleotide substitutions than normozoospermic men. However, there were no significant differences in the frequencies of nucleotide substitution and POLgamma genotypes in the two groups of men.

Item Type:Articles
Additional Information:Tanya Harris (nee Erasmuson) and Andrew J. Holyoake were supported by a University of Canterbury Doctoral Postgraduate Scholarship. Katherine Gomas was supported by a Scholarship from the Canterbury Medical Research Foundation.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Sin, Dr Angie
Authors: Harris, T. P., Gomas, K. P., Weir, F., Holyoake, A. J., McHugh, P., Wu, M., Sin, Y., Sin, I. L., and Sin, F. Y. T.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:International Journal of Andrology
Publisher:Wiley
ISSN:0105-6263
ISSN (Online):1365-2605
Published Online:20 February 2006

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