WNT4 (rs7521902 and rs16826658) polymorphism and its association with endometriosis – A systematic review and meta-analysis

Importance: This systematic review supports the involvement of the WNT4 gene in the pathophysiology of endometriosis. Objective: To conduct a systematic review and meta-analysis on WNT4 rs7521902 and rs16826658 polymorphism associated with endometriosis based on multi-ethnic case-control studies. Data sources: Comprehensive searching was performed using Medline, Embase, and Google Scholar. Study selection and synthesis: Keywords used for searching using Boolean operators are endometriosis, WNT4, and polymorphism. This review followed PRISMA guidelines, and meta-analysis was conducted in STATA18. Main outcomes: WNT4 polymorphisms identified in this review were rs7521902, rs16826658, rs2235529, rs3820282, and rs12037376. Results: A total of 250 studies were identified through databases; 10 were eligible for this review, and eight were included in the meta-analysis. Two WNT4 polymorphisms (rs7521902 and rs16826658) were analysed in the meta-analysis. A lower risk of odds in having endometriosis was apparent in the CC genotype of rs7521092 polymorphism with a pooled OR of 0.86 (0.76, 0.99). Most articles were high-quality case-control studies and were at low risk of bias. Conclusion: This study highlighted the association of WNT4 polymorphisms (rs7521092) and endometriosis across Latin America, Europe, and Asian populations. Relevance: Following the completion of the Human Genome Project, many genetic aspects of endometriosis were revealed, including the discovery of single nucleotide polymorphisms (SNPs). However, due to a lack of replications and conflicting results between studies, the conclusion of the endometriosis genetic pathway needed to be completed. This finding of WNT4 showed that its association with endometriosis was valid even in varied ethnicities, indicating a general genetic aspect of disease across populations. Nevertheless, further studies are needed to confirm this finding, including functional biological and longitudinal studies.