Genetic Variability within ADA Gene Region and Infertility in Subjects with Varicocele

A role of adenosine deaminase in male fertility is suggested by the presence of adenosine receptors in the acrosomal region of spermatozoa and in the epithelium of vas deferens. A relationship between ADA enzymatic activity and fertility in men has also been reported. We have carried a genetic study on three polymorphic sites (ADA1, ADA2 and ADA6) within the ADA gene in relation to varicocele and infertility in 136 men who were referred to the clinic for varicocele and in 246 blood donors as controls. ADA sites were studied by DNA analysis. Subjects homozygote for the three more common alleles present in the ADA sites considered (ADA1*1/*1, ADA2*1/*1 and ADA6*2/*2) were more frequent among subjects with varicocele than among controls (OR = 1.834, 95% C.I. 1.122-2.996). This phenomenon was much more marked in infertile than in fertile subjects. Subjects with this joint genotype displayed the lowest value of rectilinear sperm motility: such motility was the lowest among infertile subjects carrying the triple homozygous genotype. Many polymorphic sites have been detected within the ADA gene. It is likely that ADA variability may influence not only its enzymatic activity but also its function as an ecto-enzyme which could affect fertility in man.