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Cytochrome P450-2D6*4 polymorphism seminal relationship in infertile men.
A Zalata1, A Z El-Samanoudy, G Osman
1Medical Biochemistry Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Andrologia
|May 29, 2014
Summary
The cytochrome P450-2D6*4 wild-type allele is linked to better semen quality in infertile men. Conversely, the homozygous mutation is more common in men with poor semen parameters, indicating a potential role in male infertility.
Area of Science:
- Genetics and Reproductive Medicine
- Biochemistry and Molecular Biology
Background:
- Male infertility affects a significant portion of couples seeking reproductive assistance.
- Genetic factors, including polymorphisms in drug-metabolizing enzymes like Cytochrome P450 (CY) P450-2D6, are increasingly recognized as contributors to male reproductive health.
- The CYP450-2D6*4 polymorphism has been investigated for its potential association with various health conditions, but its specific role in semen parameters remains to be fully elucidated.
Purpose of the Study:
- To investigate the association between the CYP450-2D6*4 gene polymorphism and key semen variables in infertile men.
- To compare the frequency of CYP450-2D6*4 alleles (wild-type vs. homozygous mutation) across different categories of male infertility based on semen analysis.
Main Methods:
- Genotyping for the CYP450-2D6*4 polymorphism was performed on 308 men, categorized into fertile normozoospermia (N), asthenozoospermia (A), asthenoteratozoospermia (AT), and oligoasthenoteratozoospermia (OAT).
- Semen analysis included sperm concentration, motility, morphology, and sperm acrosin activity.
- Seminal malondialdehyde (MDA) levels were measured as an indicator of oxidative stress.
Main Results:
- The frequency of the CYP450-2D6*4 wild-type allele was higher in normozoospermic men (76.5%) compared to infertile groups (A: 70%, AT: 66.7%, OAT: 57.7%).
- Conversely, the homozygous CYP450-2D6*4 mutation was less frequent in normozoospermic men (5.9%) and more prevalent in infertile groups (A: 20%, AT: 26.6%, OAT: 26.9%).
- Men with the wild-type allele exhibited significantly higher sperm acrosin activity, concentration, motility, linear velocity, and normal morphology, along with lower seminal MDA levels, compared to those with the homozygous mutation.
Conclusions:
- The CYP450-2D6*4 wild-type allele is associated with favorable semen parameters and is more frequent in fertile men.
- The homozygous CYP450-2D6*4 mutation is linked to impaired semen quality and higher prevalence in infertile men, suggesting a potential role in male factor infertility.
- These findings highlight the CYP450-2D6*4 polymorphism as a potential genetic marker influencing male reproductive capacity.
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