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

• Published in: International journal of molecular sciences 2020-03, Vol.21 (5), p.1765
• Main Authors: Angioni, Stefano, D'Alterio, Maurizio Nicola, Coiana, Alessandra, Anni, Franco, Gessa, Stefano, Deiana, Danilo
• Format: Article
• Language: English
• Subjects: Adult; Aged; Alleles; Binding sites; Body Mass Index; Carrier Proteins - genetics; Case-Control Studies; Cell adhesion & migration; Cell Proliferation; Chromosomes; Cohort analysis; Confidence intervals; DNA Repair; Endometriosis; Endometriosis - epidemiology; Endometriosis - genetics; Female; Follicle Stimulating Hormone, beta Subunit - genetics; Follicle-stimulating hormone; Gene frequency; Gene polymorphism; Genes; Genetic diversity; Genetics; Genome-Wide Association Study; Genotype; Haplotypes; Health risk assessment; Hormones; Humans; Hypotheses; Inflammation; Italy - epidemiology; Literature reviews; Membrane Proteins - genetics; Middle Aged; Minority & ethnic groups; Molecular biology; Molecular modelling; Neovascularization, Pathologic; Nucleotides; Polymorphism; Polymorphism, Single Nucleotide; Polypeptides; Population; Population genetics; Population studies; Populations; Prospective Studies; Proteins; Risk Factors; Signal transduction; Single-nucleotide polymorphism; Steroids - metabolism; Studies; Tumors; Wnt protein; Wnt4 Protein - genetics; Young Adult
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21051765

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. 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. 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 th