Polycystic Ovarian Syndrome: We’re getting closer to how genetics causes PCOS

We’ve finally identified the genetics of polycystic ovary syndrome (PCOS), which may open the door to new treatments.

Polycystic ovary syndrome, which is thought to affect Up to 1 in 5 womendisrupts how the ovaries work, leading to at least two of three characteristics: irregular or nonexistent menstrual periods; High levels of male sex hormones, including testosterone. The accumulation of immature, cyst-like eggs in the ovaries. as a result of, Fertility problems Common with this condition.

The exact cause is unknown, but PCOS has been linked to changes in the gut microbiome and prenatal hormonal imbalances. It also runs in families, with studies estimated at approximately 70% of the risks to which an individual is exposed are 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 — that explain about 10% of a person’s risk.

To fill this knowledge gap, Shigang Zhao He and his colleagues at Shandong University in Jinan, China, analyzed the genomes of more than 440,000 women across China and Europe, 25,000 of whom had been diagnosed with PCOS, while the rest had not, in the largest genetic analysis of the condition to date.

The team identified 94 genetic variants that appear to influence the risk of developing PCOS, 73 of which had not been previously identified. One of the most interesting of these variants occurs in the gene coding for the mitochondrial ribosomal protein S22, which helps mitochondria, the energy-generating parts of cells, function properly, says Zhao. While previous studies have linked Polycystic ovary syndrome due to dysfunctional mitochondriaHe says this is the first look at how genetics might be behind this.

Another newly identified variant that affects a protein called sex hormone-binding globulin, which regulates the activity of sex hormones, is common. It is found in low levels in people with polycystic ovary syndrome.

Many remaining variables 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 genetics drives PCOS By changing levels of sex hormones“says Zhao.

Overall, the team calculated that the 94 variables explained about 27% of the variance in PCOS risk among European participants and about 34% of the risk among the Chinese population.

“This study is important because it expands our understanding of the genetic component of the disease,” he says. Elisabeth Steiner-Victorin At the Karolinska Institute in Sweden. It also highlights the need to include diverse strains in genetic studies of PCOS, says Zhao.

In the final analysis, the researchers identified drugs that could correct the pathways affected by the variables they identified. Some of these medications are already used to treat PCOS, such as clomiphene, which stimulates the release of eggs from the ovary, a process disrupted by this condition. The team also found that betaine — which is sometimes used to treat the genetic condition homocystinuria, which can cause eye and skeletal problems — could also benefit those with polycystic ovary syndrome. Studies in mice with PCOS-like symptoms could explore this as a treatment option, says Zhao.

“Today treatment is symptom-oriented; there is no medication that can cure PCOS,” Steiner-Victorin says. Common treatments include birth control pills to regulate menstruation, or clomiphene or metformin for type 2 diabetes, which can boost fertility. But there is no single treatment that is effective for everyone. “Identifying the gene clusters that influence PCOS risk can really help us target and implement more targeted treatment for these women,” she says.

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