Endocrine Abstracts

There is strong evidence that genetic factors play an important part in the aetiology of PCOS¹ and we have have proposed that PCOS has its origin in fetal life and that, in human females, exposure to excess androgen, at any stage from fetal development of the ovary to the onset of puberty, leads to many of the characteristic features of PCOS, including abnormalities of LH secretion and insulin resistance ².

In postnatal life the natural history of PCOS can be further modified by factors affecting insulin secretion and/or action, most importantly, nutrition. In the search for genes involved in the aetiology of PCOS, the focus has been on genes implicated in folliculogenesis (but about which little is known), genes involved the androgen biosynthetic pathway and those affecting insulin secretion or action. However, the candidate gene approach has, to date, proved disappointing ³. Even those studies that have been sufficiently well powered to either identify or exclude candidate susceptibility locus (and these have been very few) have produced few positive findings. The exception are the recent reports of a candidate locus on Chromosome 19p13.2 ³ (the fibrillin-3 gene) and the FTO locus on Chr 16 ⁴.

Whilst the search for candidate genes is bound to continue, it seems increasingly likely that genome-wide association studies (of the kind that has paid dividends in searching for genes in type 2 diabetes) are are the approach that is most likely to uncover the genes contributing to PCOS, even though this will require considerable resources and very large case-control populations ³.

References: 1. Franks S & McCarthy M. Rev Endocr Metab Disord 2004 5 69–76.

2. Abbott DH, Dumesic DA & Franks S. J Endocrinol 2002 174 1–5.

3. Urbanek M. Nat Clin Pract Endocrinol Metab 2007 3 103–111.

4. Barber et al. Diabetologia 2008 51 1153–8.