Risk of cardiovascular disease and mortality among women with endometriosis: Genetic insights

Maria I. Zervou : conceptualization, design of the work, data analysis. Theoni B. Tarlatzi : data analysis, writing of the original draft. Basil C. Tarlatzis : conceptualization, design of the work, critical revision of the final version of the manuscript. George N. Goulielmos : design of the work, writing of the final version of the manuscript. All authors gave final approval and agreed to be accountable for all aspects of work ensuring integrity and accuracy.

No specific funding was received from any bodies in the public, commercial or not‐for‐profit sectors to carry out the work described in this article.

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

We read with great interest the recent article by Cavadias et al., titled “Risk of cardiovascular disease and mortality among women with endometriosis: A systematic review and meta‐analysis.” 1 The authors conducted an elegant systematic review aiming to provide a meta‐analysis of the association between endometriosis and cardiovascular diseases (CVD) and mortality. Their findings showed an association of endometriosis with an increased risk of CVD and highlighted the importance of considering cardiovascular prevention strategies for women with endometriosis. Given our long‐term interest in the investigation of the genetic components involved in the co‐occurrence of endometriosis with various complex diseases, we wish to add here some pieces of information concerning the role of various genetic and epigenetic factors in this association of endometriosis with CVD. It is worth noting that understanding this association in depth requires not only clinical and pathophysiological but also mechanistic and functional genomics research. To put all relevant data into context, we performed previously a search of the literature, aiming to investigate a potentially shared genetic background regarding the co‐occurrence of endometriosis and CVD, considering that many similarities have been observed in specific molecular and cellular pathways of the diseases under study. 2 Accordingly, we had pointed to certain genes representing risk factors for developing both conditions, which are involved in immune system deregulation, cellular proliferation, neo‐vascularization, and angiogenesis, such as vascular endothelial growth factor ( VEGF ) rs1570360, estrogen receptor 1 ( ESR1 ) (or ER‐alpha ) rs9340799, interleukin‐6 ( IL‐6 ) rs1800796, interleukin‐10 ( IL‐10 ) rs1800871, interleukin‐16 ( IL‐16 ) rs11556213, methylenetetrahydrofolate reductase ( MTFR ) rs1801133 (Ala222Val), C‐C motif chemokine ligand 21 ( CCL21 ) rs2812378, ABO /9q34.2 rs507666, and tumor protein p53 ( TP53 ) rs1042522 single nucleotide polymorphisms. 2 Furthermore, we had reported various genetic polymorphisms in noncoding RNAs related to both endometriosis and CVD development, including CDKN2B , ANRIL , CDKN2BAS , CDKN2B‐AS1 , miR23B , miR27A , miR27B , miR143 , miR145 , miR146‐a , miR196a2 , miR214 , miR331 , miR423 , miR499 , and miR3120 . 2 In the framework of the present study, we managed to identify additional gene polymorphisms that are associated with endometriosis and CVD, such as cytochrome P450 family 19 subfamily A member 1 ( CYP19A1) rs10046 and rs700518, IL‐1α rs2071373 and rs3783553, VEGF rs3025039, tumor necrosis factor‐alpha ( TNF‐α ) rs1800629, nuclear factor kappa‐light‐chain‐enhancer of activated B cells ( NF‐κB ) rs28362491, ESR1 rs2234693, forkhead box protein 3 ( FOXP3 ) rs3761548, and macrophage migration inhibitory factor ( MIF ) rs755622. 3 , 4 , 5 , 6 , 7 , 8 , 9 These genes are involved in inflammatory processes, transcription mechanisms, drug metabolism, and T‐cell activation. In conclusion, our data provide evidence for a partially shared genetic background regarding the co‐occurrence of endometriosis and CVD, thus supporting further the findings presented by Cavadias et al. 1 Therefore, a link between endometriosis and CVD from the genetic and molecular biology point of view can be considered, and it is worth noting that gynecologists have to recommend to women with endometriosis a cardiology assessment. Recognizing the challenges of the meta‐genomic era in medical sciences, we suggest that further identification of novel, shared genetic factors may help to better delineate the mechanisms leading to the clinical association of the diseases under study and result in better therapeutic management and treatment.