The role of gene polymorphisms in the pathogenesis of endometriosis

This study aims to associate particular SNP foci associated with female reproductive embryogenesis, to compare women with and without endometriosis.

Key Points

Highlight:

• Single nucleotide polymorphisms (SNPs) are the most common type of genetic variations that exist among individuals; differ only by a single nucleotide base pair and are scattered throughout the human genome. SNPs are used as a marker to locate and delineate variations of genes associated with specific disease processes and to assess the genetic similarity between individuals.
• This study does not confirm some of the previously detected SNPs and highlights the fact that the pathogenesis of endometriosis is complex.

Importance:

• Recently, genetic studies have found endometriosis has a heritable component.  Genome-wide association studies (GWAS) revealed a significant association loci including rs7521902 (near WNT4),  rs10859871 (near VEZT) and rs11031006 (FSHB gene) as endometriosis‑associated SNPs.
• This study aims to explain what influence above SNPs has on the increased risk of endometriosis seen among some patients with a family history of endometriosis in a homogenous population.

Key Results:

• A significant association was detected with the WNT4 (AC genotype) in patients with stage III and IV endometriosis only.
• Evidence for association with endometriosis was also found for the VEZT gene (AC genotype). Notably, the allelic effect was in the opposite direction compared to the original GWAS.
• A significant difference in the distribution of the FSHB SNP (AG genotype and the minor allele A) was found between women with and without endometriosis.
• The patients with endometriosis did not present any increase in genotypic or allelic frequencies of the WNT4 SNP compared to patients without endometriosis.

What’s done here?

• Specific SNP foci in three genes associated with female reproductive embryogenesis to a cohort that included women with and without endometriosis.
• Specifically, three different SNP locations at WNT4, VEZT, and FSHB genetic loci were examined.
• Surgically and histologically diagnosed 166 women with endometriosis compared to 150 control women without endometriosis; endometriosis staging was performed by revised American Fertility Society classification.

Limitations: 

• The major weakness of the study is small sample size.
• Failure to confirm previous findings is largely attributed to insufficient power, population difference, interaction with genetic and/or non‑genetic factors.

Lay Summary

Single nucleotide polymorphisms (SNPs) are the most common type of genetic variations that exist among individuals. These polymorphisms differ by a single nucleotide base pair and are scattered throughout the human genome. Scientists use SNPs as a biological marker to locate and delineate mutations or variations of genes that are associated with disease processes and to assess the genetic similarity between individuals. Most SNPs are completely harmless and do not hurt health or development. However, in some cases, mutations can cause altered or absent expression of one or more genes that lead to adherent cellular processes.

Endometriosis is a gynecologic disorder that is characterized by the presence of functional endometrial tissue outside of the uterus. Recently, genetic studies have found endometriosis has a heritable component. This study aims to explain what influence SNPs have on the increased risk of endometriosis seen among some patients with a family history of endometriosis. Specifically, they looked at three different SNP locations at WNT4, VEZT, and FSHB genetic loci. The study included 166 women with surgically and histologically diagnosed endometriosis and 150 control women without endometriosis. Staging of endometriosis was performed according to the revised American Fertility Society classification.

A significant association was detected regarding the WNT4 gene (AC genotype) in patients with stage III/IV endometriosis. (P=0.0359). Additionally, a significant difference was found in the frequency of AC genotype in patients and controls (P=0.01) of the VEZT gene. For the FSHB SNP, a decreased frequency of the GA genotype was found in patients with endometriosis compared with controls (P=0.0438). No association between the FSHB SNP and endometriosis was revealed after an analysis conducted according to stages III/IV of the disease (P=0.5) for the GA genotype and allele A.

This study was aimed at exploring the presence of susceptibility genes involved from SNP polymorphisms among three genes implicated in female reproductive development. This study highlights the fact that the pathogenesis of endometriosis is complex and is compounded by the fact that SNPs are variable among individuals. Although GWAS have detected many endometriosis susceptibility genes, it is clear that there are differences in genetic associations with endometriosis across different world populations that necessitates more studies for clarification.

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/28901453