Could Endometriosis-Related Infertility Be Genetic?

Researchers identified new candidate genes associated with endometriosis-related infertility.

Key Points

Highlights:

• Researchers identified new candidate genes that could be associated with endometriosis-related infertility 

Importance:

• Genetic factors have been correlated with susceptibility to endometriosis, however, the genetic mechanisms involved in the development of infertility in women with endometriosis need to be clarified.

What's done here:

• A genetic association study to investigate the frequency of SNPs in three genes that were identified in a previous study.
• 394 infertile women with endometriosis (197 with mild, and 197 with moderate-severe), and 650 fertile controls were examined for the frequency of the genes called KAZN, LAMA5, and TAC3 using the peripheral blood samples. 
• The technique used was TaqMan allelic discrimination assays and statistical analyses were performed.

Key results:

• There was a statistically significant difference in allelic distribution in the KAZN gene between infertile women with endometriosis and control fertile women. However, this was only the case for endometriosis grades 1 and 2. 
• There was also a statistically significant difference in allelic distribution in the LAMA5 gene between infertile women with endometriosis grades 3 and 4 and control women.
• There were no differences in genotype and allelic distribution in the TAC3 gene between the two groups of women.

Limitations:

• Because the fertile control women did not have endometriosis, this study cannot tell whether the genetic polymorphisms observed are associated with endometriosis or infertility. 

Lay Summary

Researchers identified genetic polymorphisms or individual differences in two genes called AMA5 and KAZN among women with endometriosis who were infertile and control women who were fertile.

The identification of these polymorphisms could help scientists better understand why some women with endometriosis are infertile. This could ultimately help them develop new ways to target these genes in order to treat endometriosis-associated infertility.

Infertility is one of the main symptoms of endometriosis with women with the disease having a significantly lower chance of getting pregnant compared to those without the disease. 

A previous study had identified so-called single nucleotide polymorphisms or single letter changes that do not cause mutations in the DNA of women with endometriosis who were infertile, and control women who were fertile. Some of these polymorphisms were on genes that are known to be involved in the pathogenesis of endometriosis.

The same team of researchers led by Dr. Caio Parente Barbosa at Faculdade de Medicina do ABC in Brazil wanted to confirm these results. So they conducted a genetic association study in a bigger group comprising 394 infertile women with endometriosis and 650 fertile control women. They looked at the frequency of three single nucleotide polymorphisms in three genes called KAZN, LAMA5, and TAC3. These were among the genes that the researchers had identified in the previous study as carrying a single nucleotide polymorphism.

Using a technique called TaqMan allelic discrimination assays, the researchers identified a single letter difference in the KAZN and LAMA5 genes of infertile women with endometriosis compared to the DNA of fertile control women. There were no differences in the TAC3 gene of the two groups of women. 

“…[The] individual genotyping of a larger sample of patients and controls confirmed the association among KAZN and LAMA5 with endometriosis-related infertility,” the researchers wrote. They added that this the genetic analysis of these two groups of women “revealed new candidate genes contributing to the condition”.

The study was published in the scientific journal Gynecological Endocrinology.  

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/30044155