Scientists have identified a common genetic variant among women with polycystic ovary syndrome (PCOS) which may be responsible for the disorder. The genetic alteration was found to induce high levels of hormone testosterone responsible for the syndrome.
Polycystic ovary syndrome affects nearly five to fifteen percent of pre-menopausal women worldwide and is the main cause of infertility and type 2 diabetes in women. It is a now a common condition and is thought to be developed due to an imbalance of reproductive hormones that negatively affects how eggs develop in the ovaries.
Now using whole-genome sequencing techniques, the researchers from New York and Chicago have observed a significant association between the rare variant of DENND1A and reproductive and metabolic traits seen in PCOS families. DENND1A is a gene that is involved in the production of male hormones and was identified to be a key regulator of human ovarian androgen biosynthesis.
The study involved 261women from 62 families with PCOS. The participants were aged 14 to 63 years old. The families included were Caucasian and had European ancestry.
The researchers say that the findings contribute additional evidence that DENND1A plays a central role in PCOS and suggest that rare non-coding variants contribute to the disease pathogenesis.
“Our findings provide important new insights into the mechanisms by which genetic variation causes PCOS. The rare genetic variants we found may be much better for predicting the condition than the common variants. Targeting pathways regulated by this gene could lead to new therapies for the condition.” said lead researcher Andrea Dunaif, from the Icahn School of Medicine at Mount Sinai in New York,
Previously studies that investigated the role of DENND1A in ovarian androgen biosynthesis have revealed that the biologic pathway is interrupted in cases of polycystic ovary syndrome.They found that DENND1A encoded two transcripts, DENND1A.V1 and DENND1A.V2, the latter of which was found in ovarian cells and was linked to increased androgen production.
Genetics along with high levels of androgens (male sex hormones including testosterone) in women and high levels of insulin are commonly believed to cause polycystic ovary syndrome.
The condition can result in irregular periods that may lead to infertility or cysts in the ovaries. Symptoms of polycystic ovary syndrome include hirsutism, a condition in which women develop excess hair on their faces, chin, or on parts of the body. Conversely, thinning hair and male-pattern baldness can also be experienced, along with acne, weight gain, and skin tags.
“The hope would be that with genetic testing we may be able to identify high-risk people and start measures early.”said Andrea Dunaif.
“When we understand the genetic pathways that are involved, we can develop drugs to target them. If we understand that, then we may be able to come up with ways to alter the increase in DENND1A activity that happens in PCOS and treat the disease itself and even cure a number of patients.”
The study also found that other genes were also involved among the top gene associations, but were not highly significant genome-wide. These genes included C9orf3, HMGA2, ZBTB16, TOX3, and THADA.
The study has been published in the Journal of Clinical Endocrinology and Metabolism.
“We hope our results will help uncover some of the involved hereditary mechanisms and ultimately teach us more about the molecular drivers of the disorder.” said Dunaif