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  • Title: Association of CYP1A1*2A polymorphism with male infertility in Indian population.
    Author: Vani GT, Mukesh N, Siva Prasad B, Rama Devi P, Hema Prasad M, Usha Rani P, Pardhanandana Reddy P.
    Journal: Clin Chim Acta; 2009 Dec; 410(1-2):43-7. PubMed ID: 19786002.
    Abstract:
    BACKGROUND: The CYP1A1 gene is a polymorphic gene and encodes for the CYP1A1 enzyme that catalyzes the bioactivation of polycyclic aromatic hydrocarbons (PAHs). PAHs are ubiquitous pollutants in the natural environment, which are capable of forming DNA adducts once being activated to generate DNA reactive metabolites. DNA adducts in sperm cells could be considered as a sign of severe DNA damage, which played an important role in meiotic division during spermatogenesis and could be associated with infertility. Lipophilic compounds undergo metabolic activation by phase I enzymes, which introduce a reactive center into the molecule, followed by phase II conjugation reaction resulting in a water soluble product. METHODS: We genotyped CYP1A1*2A, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in a hospital based case-control study including 206 infertile men and 230 healthy fertile (control) subjects. RESULTS: Analysis showed that CYP1A1*2A CC genotype is associated with increased risk of male infertility (OR=6.08, 95% CI=1.91-25.27), while TC genotype showed a non-significantly increased risk of male infertility (OR=1.35 95% CI=0.89-2.05). Further, when the variant genotypes were combined (CYP1A1*2A TC+CC) assuming a co-dominant allele effect, TC plus CC genotypes were also found to be significant with increased risk of male infertility (OR=1.57 95% CI=1.05-2.35 p=0.02). Allele frequencies are calculated for each genotype of CYP1A1*2A and the differences for allele frequencies between the infertile and fertile men are determined using Fisher's exact test. T and C allele frequencies in infertile men are 71% and 29% as against 80% and 20% in fertile men. The differences for allele frequencies are found to be statistically significant (p=0.002). The results showed a drastic decrease in the sperm count and motility and increase in dead sperms in CC genotype when compared to other genotypes in infertile men. CONCLUSION: Based on Indian study we conclude that CC genotype of CYP1A1 is associated in the pathogenesis of male infertility.
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