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Large Differences in Testosterone Excretion in Korean and Swedish Men Are Strongly Associated with a UDP-Glucuronosyl Transferase 2B17 Polymorphism

Department of Laboratory Medicine (J.J., L.E., N.I., M.G., A.R.), Division of Clinical Pharmacology, Karolinska Institutet at Karolinska University Hospital, SE-141 86 Stockholm, Sweden; Department of Internal Medicine (M.L., C.O.), Center for Bone Research at the Sahlgrenska Academy, The Sahlgrenska Academy at Göteborg University, SE-413 45 Göteborg, Sweden; Department. of Internal Medicine (H.-K.R.), Division of Clinical Pharmacology, Inha University Hospital, Incheon 402–751, Korea; and Department of Clinical Science (K.C.), Division of Obstetrics and Gynecology, Karolinska Hospital, 171 76 Stockholm, Sweden

Address all correspondence and requests for reprints to: Jenny Jakobsson, M.Sc., Clinical Pharmacology, C1:68, Karolinska Institutet at Karolinska University Hospital, S-141 86 Stockholm, Sweden. E-mail: jenny.jakobsson{at}ki.se.

Context: The reproductive endocrinology in Asians and Caucasians is of great interest in view of large differences in prostate cancer rate and sensitivity to pharmacological male contraception. In addition, interpretation of certain antidoping tests is confounded by interethnic variation in androgen disposition. Uridine diphosphoglucuronosyl transferases have a key role in the homeostasis and metabolism of androgens. Recently a deletion polymorphism was detected in the UGT2B17 gene.

Objective: The objective of the study was to evaluate the contribution of the UGT2B17 deletion polymorphism to the interindividual and interethnic variation of androgen metabolism and excretion.

Methods and Results: Urine from 122 Swedish and 74 Korean healthy men was analyzed for several androgen glucuronides including testosterone. The distribution of the natural logarithms of urinary testosterone concentrations showed a distinct bimodal pattern in both groups, suggesting a monogenic inheritance. When the UGT2B17 genotypes were compared with urinary testosterone levels, all of the individuals of the UGT2B17 homozygous deletion/deletion genotype had no or negligible amounts of urinary testosterone. The deletion/deletion genotype was seven times more common in the Korean (66.7%) than the Swedish population (9.3%). In addition, the Swedes had significantly higher levels of serum testosterone, compared with the Koreans.

Conclusions: Our results show that the UGT2B17 polymorphism is strongly associated with the bimodal distribution of the testosterone excretion and also with the large differences in testosterone excretion between Koreans and Swedes.

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