A first of its kind study using family base genetic analysis has confirm a gene involved in male hormone production, DENND1A, plays a major role in the development of polycystic ovary syndrome (PCOS). The discovery will enable personalize medicine approaches to PCOS, including better disease prediction. The findings are available online in The Journal of Clinical Endocrinology & Metabolism.
PCOS is among the most common endocrine conditions in reproductive age women and is the leading cause of infertility and type 2 diabetes. The cause of PCOS is unknown, but there is a strong inherit susceptibility to the disorder. A number of common PCOS genetic variants that slightly increase disease risk have map in previous genome wide association studies; however the genes find to date account for only a small amount of PCOS disease risk.
PCOS is a major cause of female infertility and is associate with other serious health problems; so they said one of the lead authors of the study, Andrea Dunaif, MD, Chief of the Hilda and J. Lester Gabrilove Division of Endocrinology, Diabetes and Bone Disease at the Icahn School of Medicine at Mount Sinai.
Their findings provide important new insights into the mechanisms by which genetic variation causes PCOS. The rare genetic variants they find may be much better for predicting the condition than the common variants. Further, targeting pathways regulate by this gene could lead to new therapies for the condition.
Researchers explore the genetic basis
In the study, the researchers explore the genetic basis of PCOS by conducting whole genome sequencing on DNA from the members of 62 families of women with PCOS. These families include both parents and one or more reproductive age daughters with PCOS as well as unaffected daughters.
Bioinformatic analyses were perform to determine which genes contain variants that were likely to be damaging. Only genes that were inherit from a parent were include for further analysis. Dr. Dunaif and her colleagues found that reproductive and metabolic hormone levels were associate with rare genetic variants in DENND1A in approximately half of the families.
So this gene is important in testosterone production in the ovary; increase ovarian testosterone production is a major hormonal abnormality in PCOS. The findings indicate that this type of genetic variation contributes to the distinctive hormonal profile of the disorder.
After sequencing the entire genomes of many families affect by the disease, this has enable to study how certain rare genetic variants are associate with PCOS,” said Geoffrey Hayes, Ph.D., Associate Professor in the Department of Medicine Endocrinology, Metabolism and Molecular Medicine at Northwestern University Feinberg School of Medicine, and co-lead lead author of this study.