POLYMORPHISM IN THE CYTOCHROME-P450 2E1 GENE AND ALCOHOL-INDUCED DISORDERS OF HUMAN SPERMATOGENESIS

The association between alcohol-induced of human spermatogenesis and f our restriction fragment polymorphisms (DraI, MspI, PstI and RsaI) of the cytochrome P450 2E1 gene was investigated in an autopsy study on 2 54 men. Acquaintances were interviewed and the mean daily alcohol cons umption of the subjects was calculated on the basis of the interviews. Spermatogenesis score and testicular morphology were assessed by ligh t-microscopy, and cytochrome 2E1 polymorphic genotypes were determined using the polymerase chain reaction. Of the 204 heavy-drinking men 42 (20.6%) men had normal spermatogenesis (p<0.001, compared to moderate drinkers). Partial spermatogenic arrest was observed in 76 (37.3%) me n and complete spermatogenic arrest in 79 (38.7%) men (p<0.001, compar ed to moderate drinkers), whereas seven men (3.4%) had Sertoli cell on ly syndrome. The overall allelic frequencies for the common and rare p olymorphic alleles were 0.98 and 0.02 (MspI) and 0.99 and 0.01 (PstI a nd RsaI), respectively. No associations between heterozygosity in the MspI, PstI or RsaI loci, or the allelic frequencies of common and rare alleles, and disorders of spermatogenesis were observed. The allelic frequencies for the common and rare polymorphic alleles in the DraI lo cus were 0.90 and 0.10, respectively. No significant difference was ob served, either among moderate or heavy drinkers, in the frequency of t he rare allele between men with disorders of spermatogenesis and those with normal spermatogenesis in the respective group, although men wit h disorders of spermatogenesis in general had a slightly lower frequen cy of the rare allele when compared to those with normal spermatogenes is. In conclusion, we were unable to demonstrate a significant associa tion between any polymorphisms in the CYP2E1 gene and disorders of spe rmatogenesis. RsaI, MspI and PstI polymorphisms were extremely rare in our population and could thus possibly be excluded as reasons for gen etic susceptibility to disorders of spermatogenesis in our series.