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Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

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Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
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Infertility in Males01:23

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Male infertility affects millions of couples worldwide, arising from various factors that impact different stages of the reproductive process. An endocrine imbalance resulting from conditions like hypogonadism, Klinefelter syndrome, or pituitary disorders can disrupt hormone levels and reduce sperm production. Testicular defects, such as tumors, cryptorchidism, atrophic testes, abnormal sperm morphology, and low sperm count or motility, may arise due to genetic factors, structural...
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Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
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The human genome is over 99.9% identical between individuals, yet genetic differences exist at millions of bases. The human genome contains approximately 3 million variant positions per individual, many of which are heterozygous, contributing to genetic diversity and individual traits. Genetic variations include single-nucleotide polymorphisms (SNPs), insertions, deletions, and copy number variations (CNVs).SNPs, the most common variation, involve single-base changes in DNA. These can be...
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Genetic polymorphism in drug metabolism is crucial to the inter-individual variability observed in drug responses. Drug metabolism primarily involves the chemical modification of drugs and other xenobiotics to enhance their elimination by increasing their polarity. Two main classes of enzymes mediate this biotransformation process: Phase I enzymes, primarily cytochrome P450s, catalyze oxidation and reduction reactions, while other enzymes, such as esterases, mediate hydrolysis, and Phase II...
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Spermatogenesis is the process by which haploid sperm cells are produced in the male testes. It starts with stem cells located close to the outer rim of seminiferous tubules. These spermatogonial stem cells divide asymmetrically to give rise to additional stem cells (meaning that these structures “self-renew”), as well as sperm progenitors, called spermatocytes. Importantly, this method of asymmetric mitotic division maintains a population of spermatogonial stem cells in the male...
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[Protamine gene polymorphisms and male infertility].

Wei-jun Jiang, Jing Zhang, Xin-yi Xia

    Zhonghua Nan Ke Xue = National Journal of Andrology
    |January 29, 2016
    PubMed
    Summary

    Protamine gene (PRM) variations impact male fertility. Certain PRM polymorphisms increase infertility risk, while others offer protection, highlighting their crucial role in reproductive health.

    Area of Science:

    • Reproductive Biology
    • Genetics
    • Molecular Biology

    Background:

    • Protamine (PRM) is essential for sperm development, condensing and protecting the genome.
    • PRM replaces histones during spermatogenesis, ensuring nuclear stability.
    • PRM gene polymorphisms are increasingly linked to male infertility.

    Purpose of the Study:

    • To review the current understanding of protamine gene polymorphisms and their association with male infertility.
    • To highlight specific PRM polymorphisms and their varying effects on fertility outcomes.

    Main Methods:

    • Literature review of studies investigating PRM gene polymorphisms and male infertility.
    • Analysis of reported associations between specific SNPs (e.g., rs2301365, rs737008, rs1646022) and fertility.

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  • Examination of the relationship between PRM1/PRM2 ratio and male infertility.

    • Main Results:

    • The rs2301365 PRM polymorphism is identified as a significant risk factor for male infertility.
    • PRM1 (rs737008) and PRM2 (rs1646022) polymorphisms act as protective factors against infertility in Asian populations.
    • The ratio of PRM1 to PRM2 expression is strongly correlated with male infertility.

    Conclusions:

    • PRM gene polymorphisms play a critical role in male fertility.
    • Specific PRM variants can either increase or decrease the risk of infertility.
    • Further research into PRM genetics is crucial for understanding and potentially treating male infertility.