News & Research

    Massachusetts General Hospital Biostatistics, Boston, Massachusetts

The Genetics of Polycystic Ovary Syndrome

General Research Subject: Insulin Resistance Pre Diabetes

Focus: Adipocytes, Genetics, Integrated Physiology\Insulin Resistance

Type of Grant: Clinical Translational Research

Project Start Date: January 1, 2010

Project End Date: December 31, 2013

Research Description

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive age women. Women with PCOS have a high risk of prediabetes, type 2 diabetes and heart disease. The investigators have found a possible change in the DNA (genes of the body that encode all of our traits) that seems to be related to insulin resistance. The investigators will examine this DNA change further.

First, the investigators will try to determine the gene that this DNA change is affecting. Second, the investigators will determine what changes in a woman's hormones and diabetes hormones are affected by the change in the gene. Third, the investigators will try to determine whether the change in the gene affects a woman's ability to respond to a common treatment for PCOS, metformin.

These studies will uncover the change in a gene that might be one of the causes of PCOS. Discovering this gene will help better understand the diabetes and insulin abnormalities that are common in PCOS and will help us to better diagnose and treat PCOS to prevent the diabetes in these women.

Researcher Profile

What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?

My laboratory is interested in polycystic ovary syndrome. The disorder affects 1 in 10 reproductive age women and is therefore one of the most common hormone disorders in young women. Polycystic ovary syndrome was initially described based on the irregular menstrual cycles and infertility that these women experience. However, it soon became clear that women with polycystic ovary syndrome have an increased rate of prediabetes, type 2 diabetes and heart disease compared to women without the syndrome, even when matched for body mass index.

We are studying the genetics of polycystic ovary syndrome. We have identified a genetic marker that appears to increase the risk of having polycystic ovary syndrome. The marker sits near two genes. One of the genes is related to inflammation, which can be involved in high insulin levels and risk for diabetes. The other may be involved in the development of fat in the body.

Our study will determine how the risk for polycystic ovary syndrome is related to the genetic marker we discovered. We will determine which one of these two genes is involved in the disorder. Figuring out the gene involved will help determine new mechanisms that may cause the development of diabetes in women. The genetic marker may be useful to predict the risk for polycystic ovary syndrome so that we can start preventive measures early to avoid additional risk factors such as obesity and lack of exercise, which may accelerate the development of diabetes in these women. Finally, understanding the genes involved in polycystic ovary syndrome and its risk for diabetes may help us develop new treatments.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond?

We will use genetic markers to determine women who are at risk for developing polycystic ovary syndrome and therefore diabetes. Knowing that a woman is at risk for polycystic ovary syndrome will help her take preventive measures to avoid the additional risk of diabetes. We also hope that finding the cause of the risk based on our genetic marker will help us develop new treatments for diabetes, especially as it affects women.

Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?

I see many patients with polycystic ovary syndrome. While many excellent physicians are eager to take care of the fertility problems that come with polycystic ovary syndrome, they are not well equipped to take care of the medical problems these women develop and their risk for diabetes. It is also frustrating to feel we are putting a band-aid on the menstrual cycle problems related to polycystic ovary syndrome, but can't explain why the woman developed it or why she has a risk for diabetes. The award will help us determine the underlying cause of polycystic ovary syndrome so that we can treat the cause rather than the effects of the disorder. The award will specifically allow us to examine patients with polycystic ovary syndrome to determine how the genes cause risk for the polycystic ovary syndrome and diabetes.

In what direction do you see the future of diabetes research going?

Genetics and risk prediction will be important in the future of diabetes. There are many gene markers that can now predict the risk of diabetes from the time of birth. With these markers in hand, we can target high risk individuals for special lifestyle modification over the lifespan to prevent the onset of diabetes. We will also be able to use preventive medications that may be developed in the future to target the individuals at greatest risk for diabetes.