Endocrine Abstracts (2012) 28 P288

Genetic variants in CYP19 associated with increased aromatase activity are not associated with male hypogonadism in type 2 diabetes

Fraser Gibb1, Brian Walker1, Rebecca Reynolds1, Mark Strachan4, Geoff Beckett2 & Jackie Price3

1Endocrinology Unit, University of Edinburgh, Edinburgh, United Kingdom; 2Clinical Biochemistry, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom; 3Public Health Sciences, University of Edinburgh, Edinburgh, United Kingdom; 4Metabolic Unit, Western General Hospital, Edinburgh, United Kingdom.

Background: Testosterone deficiency is common in obesity and in type 2 diabetes mellitus. It is hypothesised that the expanded adipose pool, which is the major source of aromatase in men, depletes testosterone levels by excess conversion to estradiol. Individuals with either the GG rs2470152 polymorphism in intron 1 or a high number of TTTA repeats in intron 4 of CYP19 are known to have greater aromatase activity with demonstrable effects upon plasma estradiol and osteoporosis risk. AIM To determine whether CYP19 variants are associated with the risk of testosterone deficiency in men with type 2 diabetes mellitus.

Methods: 425 men (mean age 68.1 y and BMI 30.2 kg/m2) from the Edinburgh Type 2 Diabetes Study had early morning plasma testosterone levels measured by ADVIA Centaur immunoassay. TTTA repeat number was established using PCR. The rs2470152 SNP was genotyped by TaqMan assay PCR.

Results were analysed by ANOVA using SPSS (v19).

Results: Subnormal total testosterone levels (<10 nmol/l) were observed in 33.6% of patients, with low levels of calculated free testosterone (<245 pmol/L) in 57.2%. Neither TTTA repeat copy number nor rs2470152 genotype were associated with either total or free testosterone levels. Men categorised as testosterone deficient were no more likely to be GG homozygotes or to have high TTTA repeat numbers.

Discussion: The apparent absence of an effect of CYP19 genotype on testosterone levels could be interpreted as evidence that aromatase is not a key mediator of hypogonadism in this population. The study was adequately powered (80%) to detect a difference in testosterone of 2.2 nmol/l between genotype 1–1 and 2–2, however, the effect of genetic variation may be marginal in the context of an expanded adipose pool and the confounding co-morbidities that may contribute to androgen deficiency in this cohort. Reassessment of the influence of CYP19 variants in a younger population may be of value.

Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding: Declaration of Funding: Wellcome Trust.

Mean (±GSEM) values categorised by TTTA repeat genotype group (1=allele with repeat number >9.2=repeat number <9) and by rs2470152 genotype.

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