An illustration of polycystic ovary syndrome, in which the ovaries become enlarged.
Scientific photo library / Alamy
We've finally figured it out genetics polycystic ovary syndrome (PCOS), which could open the door to new treatments.
PCOS, which is believed to affect up to 1 in 5 womendisrupts the functioning of the ovaries, leading to at least two of three symptoms: irregular or absent menstruation; increased levels of male sex hormones, including testosterone; and a collection of immature eggs, similar to cysts, in the ovaries. As a result, fertility problems are common to this condition.
Its exact cause is unknown, but PCOS has been linked to changes in the gut microbiome And hormonal imbalance before birth. This is also works in familiesAccording to research, this is approximately 70 percent of an individual's risk is due to genetics. But so far, researchers have identified only about 25 genetic variants involved in the production of sex hormones such as estrogen and testosterone and ovarian function, which explain about 10 percent of a person's risk.
To fill this knowledge gap, Shigang Zhao at Shandong University in Jinan, China, and colleagues analyzed the genomes of more than 440,000 women in China and Europe, 25,000 of whom were diagnosed with PCOS and the rest were not, in the largest genetic analysis of the disease to date.
The team identified 94 genetic variants that appear to influence the risk of PCOS, 73 of which had not previously been identified. One of the most interesting of these variants occurs in the gene encoding mitochondrial ribosomal protein S22, which helps mitochondria, the energy-generating parts of cells, function properly, Zhao says. Although previous studies have linked PCOS to dysfunctional mitochondria“This is the first look at how genetics may be behind this,” he says.
Another recently identified variant affects a protein called sex hormone binding globulin, which regulates the activity of sex hormones and usually occurs at low levels in people with PCOS.
Many of the remaining variants affect the function of ovarian granulosa cells, which produce estrogen and progesterone and help eggs develop, during the menstrual cycle. This supports the idea that PCOS is caused by genetics. by changing the level of sex hormones” says Zhao.
Overall, the team estimated that the 94 variants explained about 27 percent of the variation in PCOS risk among European participants and about 34 percent of the risk among the Chinese population.
“This study is important because it expands our understanding of the genetic component of the disease,” says Elisabeth Stener-Victorin at the Karolinska Institutet in Sweden. “This also highlights the need to include diverse ancestral populations in genetic studies of PCOS,” says Zhao.
In the final analysis, the researchers determined drugs this could correct the pathways affected by the variants they identified. Some are already used to treat PCOS, such as clomiphene, which stimulates the release of eggs from the ovary, a process that is disrupted by the disease. The team also found that betaine, which is sometimes used to treat the genetic disorder homocystinuria, which can cause vision and skeletal problems, may also benefit people with PCOS. Studies in mice with induced PCOS-like symptoms could explore this as a treatment option, Zhao said.
“Today, treatment is focused on symptoms; there is no medicine that can cure PCOS,” says Stener-Victorin. Common treatments include birth control pills to regulate menstrual cycles, clomiphene, or the type 2 diabetes drug metformin, which can improve birth rate. But no treatment is effective for everyone. “Identifying gene clusters that influence the risk of PCOS could really help us guide and provide more targeted treatments for these women,” she says.
Topics:
