Genes Linked to Both Infertility and Heart Problems, Cancer in Females

Genetic diseases from common conditions like heart disease to rare neurological problems like Amyotrophic lateral sclerosis (ALS) are high among about 17% of women with unexplained infertility, reports Medical College of Georgia researchers. The researchers aimed to know about the prevalence of disease-causing genetic variants in females with unexplained infertility and published their study findings in the New England Journal of Medicine. This study is the first of its kind.

They conducted the study based on the assumption that genetic disease creates a predisposition to infertility and subsequent medical illness and their findings support that link. Females with infertility have been noted to have an increased risk of cardiovascular disease.

While clear, common pathways between infertility and conditions like heart disease, still have not been established, a strong association between infertility and future disease can still assist in early detection, genetic counseling, and intervention. Fertility could be in effect a “biomarker” for future medical illness.

Unexplained Female Infertility Associated with Genetic Disease Variants

They sequenced the protein-coding regions of genes, of 197 females ages 18 to 40 with unexplained infertility, a percentage that comprises about 30% of infertile females, to look for variants in genes that were known or suspected to cause disease. A group of some 900 couples from multiple institutions with no obvious cause for infertility, like problems with ovulation or unhealthy sperm.

They found 6.6% of the females they studied had variants in 59 genes termed “medically actionable,” which means they are likely to cause conditions like heart disease and breast cancer but there are interventions, lifestyle and/or medical, that might remove or at least reduce their risk. By comparison, about 2.5% of the general population has been found to have variants in these genes.

An additional 10% of the females had gene variants known to cause diseases for which little to no action could be taken to ameliorate the problem, like Parkinson’s disease. They found 14 variants of the medically actionable genes in 13 of the females; one woman had two variants.

Those included relatively well-known variants, like four women with variants of BRCA1 and BRCA2, which are associated with a high risk of breast or ovarian cancer. Six females had variants in five genes associated with the increased risk of cardiovascular disease, things like having a genetic predisposition to high cholesterol levels and irregular heart rhythms, some of which can be lethal.

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One female had a variant in the gene MYH11, which is associated with an increased risk of a rupture of the aorta, the largest blood vessel in the body. Numerous rare variants of uncertain significance also were found in the medically actionable genes.

Additionally, they found 20 variants in 21 other females in genes associated with conditions that likely could not be mitigated, like a dramatically increased risk of developing muscle wasting ALS, or Lou Gehrig’s disease, and kidney-destroying polycystic kidney disease, which will ultimately require dialysis and/or a kidney transplant.

Is Genetic Testing Must for Unexplained Infertility in Women?

While more study is needed before moves are made like recommending genetic testing for all females or males with unexplained infertility, researchers say their findings support the notion that the higher incidence of future medical problems in these women may have a genetic component.

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Now, genetic testing for infertility is done selectively. The new study provides more evidence that genetic testing might need to be considered a handful of years down the road if findings continue to hold.

Another area that needs further exploration is whether some of the gene variants may be causative of both infertility and disease. Researchers also hope that the new findings will inspire others to further explore whether the disease-causing variants they found present in these females also are factors in their infertility.



Source-Eurekalert