B. Yu et Dj. Handelsman, Pharmacogenetic polymorphisms of the AR and metabolism and susceptibility to hormone-induced azoospermia, J CLIN END, 86(9), 2001, pp. 4406-4411
Clinical trials of hormonal male contraceptive regimens have identified a c
onsistent population polymorphism in susceptibility to hormone-induced azoo
spermia. Using identical hormonal regimens, fewer men of European origin (a
pproximately two thirds) become azoospermic compared with Asian men who vir
tually all become azoospermic. This variation within and between population
s remains unexplained. To investigate pharmacogenetic differences in androg
en metabolism or action that might explain variable susceptibility to hormo
nal. induced azoospermia, we studied single nucleotide polymorphism in the
CYP3A4 gene, which encodes the major hepatic T-inactivating enzyme, and CAG
and GGC triplet repeats in the AR gene in 75 Australian volunteers partici
pating in a male hormonal contraceptive study and 106 population controls.
These men were classified into groups according to whether 6 months of week
ly T enanthate injections produced azoospermia (n = 54), near-azoospermia (
n = 7), and non-azoospermia (n = 14). Mutagenically differentiated PCR was
designed to identify A/G variants in the promoter region of the CYP3A4 gene
. Fluorescent-labeled DNA fragments containing either CAG or GGC repeats we
re amplified from the genomic DNA, and their sizes were determined based on
the capillary electrophoresis. The G allele of CYP3A4 gene was absent from
the nonazoospermia and near-azoospermia groups, but overall this single nu
cleotide polymorphism distribution did not differ significantly between men
in the azoospermia group or population controls. There were no significant
differences in distribution of CAG and GGC triplet repeats among three gro
ups or between them and the population controls based on the maximum likeli
hood estimate of the odds ratio and CLUMP II analyses. These results sugges
ted that neither genetic polymorphisms in the AR gene (CAG and GGC repeats)
nor that in hepatic androgen metabolism (CYP3A4 A/G variant) were the majo
r contributors to the within-population variations in susceptibility to T-i
nduced azoospermia.