Association between interleukin-10 promoter polymorphisms and endometriosis: A meta-analysis
Highlights
► IL-10 − 592 A/C polymorphisms showed a significant increased risk of endometriosis. ► IL-10 − 1082 A/G and 819 T/C polymorphisms showed no association with endometriosis. ► IL-10 − 592 A/C polymorphisms was not associated with the severity of endometriosis.
Introduction
Endometriosis is a common gynecologic disorder in women of reproductive age and may cause pelvic pain and infertility. Endometriosis is characterized by the implantation and growth of endometrial tissue outside the uterine cavity. It is reported to occur in around 10% of women of reproductive age and in 30–50% of infertile women (Cramer and Missmer, 2002). The importance of endometriosis is reflected in the growing number of studies published on the subject over the past 20 years in which particular emphasis has been given to investigate the pathogenesis of the disease. The exact etiology and pathogenesis of endometriosis are unclear, but both environmental and genetic factors have been implicated in the disease. Various theories have been proposed to explain the pathogenesis of endometriosis, but its overall etiology has not yet been established. Family studies of endometriosis indicate that close relatives of patients with endometriosis have an increased risk for the disease, suggesting that genetic components perhaps contribute to endometriosis (Kennedy, 1999). Recently, several lines of genetic-association studies have revealed associations between the development of endometriosis and certain genetic polymorphisms (Chun et al., 2012, Gallegos-Arreola et al., 2012, Luisi et al., 2006), although the genes that play a role in susceptibility to the development and progression of endometriosis are unknown.
Cytokine mediated immune and inflammatory responses have been considered to play an important role in the pathogenesis of endometriosis (Wu and Ho, 2003). In recent years, it has been suggested that endometriosis is an inflammatory disease involving a possible shift towards Th2 immune response component. It was reported that Th2 cytokine (IFN-gamma and interleukin-10) levels were significantly higher in the peritoneal fluid of patients with endometriosis compared to those without endometriosis, and there was a significant shift towards Th2 immune response in patients with endometriosis (Podgaec et al., 2007).
Interleukin (IL)-10 is an obvious candidate for investigation. IL-10 is a critical anti-inflammatory cytokine that is known to suppress Th1-like immune responses and promote Th2 responses. IL-10 is produced by Th2 cells, B cells, monocytes, and macrophages. IL-10 also plays a role in the development and progression of endometriosis. The levels of IL-10 in peritoneal fluid are significantly increased in patients with endometriosis compared with controls, and increased IL-10 production may partially contribute to the disturbed immune regulation in patients with endometriosis (Ho et al., 1997, Punnonen et al., 1996). The IL10 gene maps to chromosome 1q31–q32 (Eskdale et al., 1997). Twin studies and family studies have suggested that more than 70% of the variation in IL-10 production is genetically determined (Westendorp et al., 1997). Previous in vitro studies using peripheral blood mononuclear cells have suggested that IL-10 − 1082 G/G, − 819 C/C and − 592 C/C genotypes are associated with higher IL-10 production than other genotypes (Turner et al., 1997).
Numerous illnesses have been related to IL-10 gene promoter polymorphisms. In recent years, the relationship between endometriosis and polymorphisms at positions − 1082 A/G, − 819 T/C and − 592 A/C (Riiskjaer et al., 2011, Xie et al., 2009) in the promoter region of the IL-10 gene has been analyzed, although a clear role for these genetic variants is not established. However, the genetic association studies that examined whether polymorphisms in the promoter region of the IL-10 gene are associated with endometriosis have provided controversial or inconclusive results, partly because each study involved few cases and few controls and, therefore, there was not enough information to demonstrate association. To shed some light on these contradictory results, as well as to decrease the uncertainty of the effect size of estimated risk, a meta-analysis of all of the available studies related the polymorphisms in the promoter region of the IL-10 gene and their associations with endometriosis susceptibility was carried out.
Section snippets
Literature search strategy
The PubMed, Embase, HuGE Navigator (http://www.hugenavigator.net/) (Lin et al., 2006) and China National Knowledge Infrastructure (CNKI) were searched to retrieve all papers available, without language restrictions, using both free words and index terms specific to each search platform (MeSH in PubMed and Emtree in Embase). The search strategies were based on combinations of the keywords (‘interleukin-10’ or ‘IL10’) and (‘polymorphism’ or ‘genotype’ or ‘genetic’) and (endometriosis). The
Studies selection and overview of the study characteristics
A total of 55 publications were generated by the search strategy. After careful examination using eligibility criteria, eight case–control studies which examined the association between the IL-10 gene promoter polymorphisms and the susceptibility to endometriosis were finally included in the meta-analysis (He et al., 2009, Hsieh et al., 2003, Juo et al., 2009, Kitawaki et al., 2002, Li and Xie, 2010, Riiskjaer et al., 2011, Xie et al., 2009, Zhang et al., 2007). Of the eight selected studies,
Discussion
Interleukin-10 is an important immunomodulatory cytokine. In several meta-analysis studies, the IL-10 gene promoter polymorphism has been shown to be associated with several pathological processes, such as pulmonary tuberculosis (Pacheco et al., 2008), systemic lupus erythematosus (Nath et al., 2005), gastric cancer (Zhuang et al., 2010), and rheumatoid arthritis (Lee et al., 2012).
Although the multifactorial nature of endometriosis is well recognized, genetic factors are considered to be
Authors' roles
Wei Fan designed and performed the study, collected and analyzed the data, wrote the paper, and reviewed/edited the manuscript. Shangwei Li reviewed/edited the manuscript. Qiong Chen collected and analyzed the data. Zhongying Huang designed the study and reviewed/edited the manuscript. Qianhong Ma reviewed/edited the manuscript. Zhun Xiao collected and analyzed the data.
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