2.4.7. Genetics of PCOS
A genetic basis for the Stein-Leventhal syndrome was suggested by Cooper and colleagues in 1968 (Cooper et al. 1968). They studied 18 families in which the syndrome appeared in a pattern consistent with a dominant mode of inheritance. Many later studies have also suggested a dominant mode of inheritance (Ferriman & Purdie 1979, Hague et al. 1988, Lunde et al. 1989, Carey et al. 1993, Govind et al. 1999) and one study suggested an X-linked mode (Givens 1988). There are obvious problems which make genetic studies of PCOS difficult to perform. The heterogeneity and lack of universally acceptable clinical or biochemical diagnostic criteria have been discussed. PCOS is a disorder which primarly affects women of reproductive age and it is therefore difficult for segregation studies to span more than one generation. There is no commonly accepted male phenotype. Male pattern premature balding has been demonstrated in male relatives in familial PCOS studies. Lastly, the high prevalence of PCO in the population means that large pedigrees may include subjects with PCO arising from a different genotype than that of the proband (Franks et al. 1997).
Genetic analyse of candidate genes have been performed. Both linkage and association studies have suggested that PCOS can be explained by the interaction of a small number of key genes with environmental, particularly nutritional, factors. The steroid synthesis gene CYP11a, coding for P450 cholesterol side chain cleavage and the insulin gene regulatory region may be involved (Franks et al. 1997, Waterworth et al. 1997, Diamanti-Kandarakis et al. 2000).
While we are unable to exclude an autosomal or X-linked dominant mode of inheritance, the heritability of PCOS is probably more complex, similar to that of type 2 DM or cardiovascular disease. However, a positive family history appears to be the most informative risk factor for the development of PCOS (Azziz & Kashar-Miller 2000). Furthermore, environmental factors alter the clinical and biochemical presentation in those with genetic predisposition to PCOS. This is illustrated by the effect of obesity, or conversely calorie restriction, on insulin levels, insulin sensitivity and menstrual function (Dunaif et al. 1987, Holte et al. 1995).
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PCOS and Genetics (short easy read) 
