PCOS and Genetics [Part 2]
PCOS and Genetics [Part 2]
What are the genes involved in PCOS?
Hello everyone,
I hope you enjoyed learning how genetics work in the past newsletter. We mentioned that there are genes involved in PCOS. In today’s newsletter, we deep-dive into the most important ones.
Before we get started, please note that because they have found these variations in women with PCOS, it doesn’t mean YOU have it. These are genes that showed up when they looked at the genes of women with PCOS. Given the manifestation of PCOS is so diverse, you also can expect variations in these genes. The only way to know yours is to test your genes.
If you are interested in testing your genes, I have partnered with the team at Team Gene. This is where I get all my genetic tests done. Drop me a message by replying to this email and I will send you the details.
In this newsletter:
Genes involved in weight gain
Genes involved in high testosterone
Genes involved in LH and FSH
Genes involve in insulin and action
Every disease has a genetic component. In some diseases, such as breast cancer, the genetic component is a bit stronger than in others (55%–72% of women who inherit a harmful BRCA1 variant might develop it.). However, other genetic variations, such as some of the ones we will discuss today, have a lesser strong effect on our health. We do not typically think of these diseases as "genetic diseases" because we inherit not the certainty of developing a disease but only a predisposition to it.
PCOS Genetics - Epigenetics
Apart from the errors in genes that we might have inherited from our parents directly, scientists believe that increased exposure to androgens in the belly of our mums could be the reason behind PCOS programming. Specifically, excess insulin from the mother stimulates the ovaries of the baby to produce excess androgens. This is called epigenetics. The environment is able to modify our DNA. It usually does so by either up-regulating or down-regulating specific protein productions.
The ability of our environment to “modify” our DNA is the reason why the field of epigenetics believes that we have power over our genes. Just because we have a genetic predisposition towards diseases, it doesn’t mean we will develop it. This is dependent on the environment. Leaving a lifestyle that creates an internal environment where potentially harmful DNA variables can be down-regulated means we can protect ourselves against diseases. And this is why I advocate for good nutrition, movement, sleep and calm. This is so we can create an environment where we make the most of our DNA programming.
The genes that have been found to behave differently in PCOS
A meta-analysis of studies comparing 10,000 European women with polycystic ovary syndrome (PCOS) and 100,000 controls have identified 19 DNA variations for PCOS. We won’t go through all of them, but we will cover the most important ones:
Genes involved in weight gain
FTO
The FTO gene is mainly associated with obesity and resistance to weight loss. This gene regulates our metabolism. Its full mechanism is not yet fully known, but it has been shown to be associated with PCOS.
THADA
Changes in the expression of THADA gene alter insulin secretion and insulin resistance by changing the job of the pancreatic beta cells. THADA is one of the top risk genes for type 2 diabetes, and it has also been associated with PCOS. One theory is that by adapting to warmer climates, we have reduced our metabolic rates and increased our ability to store energy (put on weight). This gene might be the one that got altered to adapt to a new, warmer environment.
Genes involved in high testosterone
We know that higher levels of testosterone are one of the drivers of PCOS.
A tiny recap, cholesterol gets converted into testosterone and testosterone to oestrogen (for the full explanation, please see here). Within these conversions, some genes are at play. Specifically, CYP17, CYP21, CYP11a, and CYP19 are involved. Please see the complicated diagram below 👇🏼
CYP17
Of these, CYP17 is the gene that codes for the conversion of cholesterol to testosterone. This means that this conversion might be up-regulated, resulting in higher levels of testosterone. We know that this is one of the main mechanisms by which PCOS develops and gives its symptoms.
CYP19
CYP19 is the gene that codes for enzymes involved in the conversion of testosterone to Estrogen. Variations of this gene have been found in women to PCOS to create a deficiency in these enzymes. This means that there isn’t enough to convert all the testosterone into estrogen, leaving us with higher levels of testosterone.
Androgen Receptor Gene (AR)
This gene codes for androgen receptors. All androgens (testosterone) transmit their signal via a receptor. Variations in this gene might be responsible for those who are experiencing symptoms of high testosterone, but it doesn’t show on blood test results. This is due to the increased activity of these receptors.
Serum Sex Hormone-Binding Globulin (SHBG)
We have discussed SHBG before in our newsletter. When the SHBG protein binds to testosterone, your organs can't use this hormone. Your tissues can only use testosterone that is "free”. Low levels of SHBG have been identified in women with PCOS. Low levels mean that testosterone travels freely through the blood in excess, interacting with things it’s not meant to. The gene that codes for this protein has been found to have variation for us.
Genes involved in LH and FSH
We know that for us to get a period and our ovaries to create the hormones they require, we need “the perfect dance” between LH and FSH. PCOS is characterised by elevated LH levels, which cause the overproduction of androgens. LH performs its function by attaching to its receptor, the Luteinizing Hormone/Choriogonadotropin Receptor (LHCGR). Guess what? Some variations in this gene might mean our ovaries are oversensitive to the action of LH.
In addition to variations in the LH, there were variations in the FSHR gene, which also codes for the FSH receptors.
Genes involved in Insulin production and action
INS VNTR, INSR, IRS-1 and IRS-2
This Insulin pathway gene variation has been found in type 2 diabetes patients. Further research also found an association with PCOS. These gene variations impact the secretion of insulin from the pancreas, the receptor receiving insulin, and the ability of cells to uptake glucose. These gene variations seem to be more present in higher BMI, insulin-resistant women with PCOS.
It was reported that one of these variations (INS VNTR) was transmitted significantly more commonly from fathers to affected daughters.
Conclusion
There is probably more than what I described here. I am deeply interested in this topic because we put a lot of pressure on our actions to solve things. But sometimes, our genes might work against us. Understanding them means we can learn how to work with what we have been given.
See you in the next one where we discuss my OWN genetic make up.
See you next Sunday!
Francesca