Associations between common variation in the aromatase gene promoter region and testosterone concentrations in two young female populations.

We recently reported association between a coding-region single nucleotide polymorphism (SNP50) in the aromatase gene that encodes a key enzyme in testosterone metabolism, with risk for the development of precocious pubarche and circulating testosterone concentrations in two independent female populations. We have now explored further association with variation in the promoter-region of the aromatase gene. We genotyped six promoter-region haplotype-tag SNPs in young women from Oxford, UK (n = 109), and in girls with precocious pubarche (n = 186) and controls (n = 71) from Barcelona, Spain. Aromatase distal promoter-region variation was associated with plasma testosterone concentrations in both Oxford (r(2) = 18.3%, p = 0.01) and Barcelona (r(2) = 8.5%, p = 0.03) females. These associations were independent of SNP50, but appeared to be dependent on different SNPs in Oxford (r(2) = 13.7%, p = 0.006 with SNPs 11 (p = 0.009), 28 (p = 0.02) and 39 (p = 0.06)) and Barcelona (r(2) = 5.9%, p = 0.002 with SNP43 (p = 0.002)) populations. Aromatase distal promoter-region variation was also associated with PCOS symptom score in Oxford women (r(2) = 14.5%, p = 0.048), but, unlike SNP50, was not associated with precocious pubarche risk in Barcelona girls. In conclusion, aromatase distal promoter-region variation appears to have functional consequences for plasma testosterone concentrations in females. The variable associations with androgen-related clinical features could possibly reflect the tissue-specific promoters of the aromatase gene.

Polycystic ovary syndrome in adolescence and early adulthood.

Polycystic ovaries and the associated syndrome are recognized as the most common cause of endocrine disturbances in adult women, but much less research has been performed to examine how polycystic ovary syndrome (PCOS) presents in girls and young women. Polycystic ovaries have been demonstrated in childhood, and there is evidence to show that even very young women may show symptoms and signs of the associated syndrome. Closer examination of younger populations (less-than-or-eq, slant 25 years of age), and in particular, studies of girls during the transition from puberty into early adulthood (adolescence), may provide new insights into the pathogenesis and natural history of polycystic ovaries and PCOS, and may indicate whether polycystic ovaries could potentially be considered as a marker for health screening. Consideration should be given to the management of girls and young women with polycystic ovaries and PCOS as this group may have different needs and health risks compared with older women.