Genetic Characterization of Endometriosis Patients: Review of the Literature and a Prospective Cohort Study on a Mediterranean Population

Abstract

The pathogenesis of endometriosis is unknown, but some evidence supports a genetic predisposition. The purpose of this study was to evaluate the recent literature on the genetic characterization of women affected by endometriosis and to evaluate the influence of polymorphisms of the wingless-type mammalian mouse tumour virus integration site family member 4 (WNT4), vezatin (VEZT), and follicle stimulating hormone beta polypeptide (FSHB) genes, already known to be involved in molecular mechanisms associated with the proliferation and development of endometriotic lesions in the Sardinian population. Materials and Methods: In order to provide a comprehensive and systematic tool for those approaching the genetics of endometriosis, the most cited review, observational, cohort and case-control studies that have evaluated the genetics of endometriosis in the last 20 years were collected. Moreover, 72 women were recruited for a molecular biology analysis of whole-blood samples—41 patients affected by symptomatic endometriosis and 31 controls. The molecular typing of three single nucleotide polymorphisms (SNPs) was evaluated in patients and controls: rs7521902, rs10859871 and rs11031006, mapped respectively in the WNT4, VEZT and FSHB genes. In this work, the frequency of alleles, genotypes and haplotypes of these SNPs in Sardinian women is described. Results: From the initial search, a total of 73 articles were chosen. An analysis of the literature showed that in endometriosis pathogenesis, the contribution of genetics has been well supported by many studies. The frequency of genotypes observed in the groups of the study population of 72 women was globally coherent with the law of the Hardy–Weinberg equilibrium. For the SNP rs11031006 (FSHB), the endometriosis group did not show an increase in genotypic or allelic frequency due to this polymorphism compared to the control group (p = 0.9999, odds ratio (OR) = 0.000, 95% confidence interval (CI), 0.000–15.000 and p = 0.731, OR = 1639, 95% CI, 0.39–683, respectively, for the heterozygous genotype and the polymorphic minor allele). For the SNP rs10859871 (VEZT), we found a significant difference in the frequency of the homozygous genotype in the control group compared to the affected women (p = 0.0111, OR = 0.0602, 95% CI, 0.005–0.501). For the SNP rs7521902 (WNT4), no increase in genotypic or allelic frequency between the two groups was shown (p = 0.3088, OR = 0.4133, 95% CI, 0.10–1.8 and p = 0.3297, OR = 2257, 95% CI, 0.55–914, respectively, for the heterozygous genotype and the polymorphic minor allele). Conclusion: An analysis of recent publications on the genetics of endometriosis showed a discrepancy in the results obtained in different populations. In the Sardinian population, the results obtained do not show a significant association between the investigated variants of the genes and a greater risk of developing endometriosis, although several other studies in the literature have shown the opposite. Anyway, the data underline the importance of evaluating genetic variants in different populations. In fact, in different ethnic groups, it is possible that specific risk alleles could act differently in the pathogenesis of the disease.

Key Promoter Region of Wnt4 response to FSH and Genetic Effect on Several Production Traits of Its Mutations in Chicken

“…There are two studies showing that SNPs of the Wnt4 gene can affect its expression and function. SNP rs7521902 in Wnt4 is significantly correlated with the pathogenesis of endometriosis (Angioni et al, 2020), and rs2072920 in Wnt4 is associated with body mass index (BMI) variations in the Han Chinese population (Dong et al, 2017). We identified the critical regions of the Wnt4 promoter which contained a SNP -3015 (G > C) and we showed that SNP -3015 (G > C) in the Wnt4 gene was significantly associated with keel length and comb length in chickens, the individuals with CG genotype having a longer keel length.…”

TLR4 T399I Polymorphism and Endometriosis in a Cohort of Italian Women

“…In previous studies of Italian cohorts of endometriosis patients, environmental factors [40], as well as different SNPs in other genes were investigated [41][42][43][44]. More recently, in a Mediterranean cohort of patients (Sardinian population), no significant association was observed for three SNPs present in WNT4, VEZT and FSHB genes (rs7521902, rs10859871 and rs11031006, respectively), which have been previously identified as risk factors for endometriosis in other populations [45]. Both negative and positive results are important to shed light on risk factors of this complex disease.…”

Prevalence of Common Gynecological Conditions in the Middle East: Systematic Review and Meta-Analysis

“…Most GWAS datasets have been generated from women of European ancestry, with only two in women of East Asian ancestry. It is important to define the extent of the effects of specific risk alleles in different ethnic groups and conduct trans-ethnic mapping to restrict signal to causal variants of endometriosis (129)(130)(131).…”