PCOS is the most common female endocrine disorder affecting some 5-15% of all women in their reproductive years. It is a notoriously heterogeneous syndrome which runs within families. It has a high degree of heritability and is currently looked upon as being a complex genetic disorder.
Several
hundreds of candidate genes have been studied however the majority of these genetic
variants have not been
replicated in sufficiently large case
control studies . Genetic variants in the fibrillin gene , the Androgen receptor, FTO gene the insulin
receptor , the FSHR gene, the
TNF alpha gene and some variants
in the lL-6 gene do
confer a certain risk for
PCOS and have been replicated in sufficiently large studies or
meta analyses.
More recently, GWAS has identified up to 20
genetic variants genes involved
in neuroendocrine, metabolic and reproductive pathways. These
studies also provided evidence
for shared biologic pathways
between PCOS and a number
of metabolic disorders
menopause depression
and male- pattern balding and a
putative male phenotype.
There
is not much of overlap between GWAS findings and most functional molecular studies. However most of the
identified SNPs seem to paly a
role in a pathway responsible for
trafficking and recycling of large
protein transmembrane receptors.
Moreover some promising SNPs
involved in gonadotropin
action have been identified which do
not only constitute risk
factors for PCOS but also
seem to influence response to ovulation induction
treatment.
Lastly but not least evidence is accumulating that epigenetic
mechanisms might as well play a role in the pathogenesis of PCOS either
during fetal programming or in later life via factors as
obesity and diet composition .
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