Functional genetic polymorphisms and female reproductive disorders: Part II--endometriosis

Abstract

BACKGROUNDEndometriosis has a strong genetic component, and numerous genetic studies have been reported.METHODSWe have systematically reviewed these studies and included 114 in our final selection.RESULTSWe found no consistent evidence linking endometriosis with specific polymorphisms in genes encoding inflammatory mediators, proteins involved in sex steroid metabolism, vascular function and tissue remodelling. Although a number of polymorphisms have been associated with endometriosis in selected populations, the associations have not been independently confirmed, either because only single studies were carried out on these markers/genes or because other studies reported no association. The most solid evidence linking specific polymorphisms to endometriosis came from studies investigating glutathione-S-transferase, a phase II detoxification enzyme. Carriage of the GSTT1 null deletion variant showed consistent association with endometriosis with a 29% increased risk; however, it cannot be excluded that this result was due to publication bias, and this association should be independently confirmed in large-scale, well-designed case–control studies.CONCLUSIONSThe evidence of an association between genetic polymorphisms and endometriosis is weak. Carriage of the GSTT1 null deletion may moderately increase the risk of this disease. We suggest that the methodology of association studies should be improved in order to identify and validate associations in endometriosis.

Nitric oxide modulates mitochondrial activity and apoptosis through protein S-nitrosylation for preimplantation embryo development

“…Furthermore, studies of single nucleotide polymorphism s reveal that GSTT1 (glutathione-S-transferase) null deletion [36] and eNOS [20] are associated with moderate risk of endometriosis. In addition, endometriosis-related infertility is associated with glutathione peroxidase activity [29].…”

“…Glutathione peroxidase activity has been implicated in endometriosisrelated infertility [29]. Furthermore, carriage of the GSTT1 (glutathione-S-transferase) null deletion is associated with moderate risk of endometriosis [36]. Antioxidant agents that can eliminate reactive oxygen species might negate the deleterious effects of NO and have beneficial effects on embryo development in vivo and ,possibly, the natural fertility of patients with minimal to mild endometriosis.…”

Effect of genetics, epigenetics and variations in the transcriptional expression of cadherin–E in breast cancer susceptibility

“…Los resultados concernientes al efecto de las variables en la región promotora del CDH1 y su asociación con el cáncer de mama no fueron suficientemente claros, por lo que es necesario determinar el efecto real de estas mutaciones en el funcionamiento de la proteína. Contrario a lo observado en este estudio, en varias investigaciones se ha asociado el polimorfismo rs5030625 con la endometriosis (24,25) y el cáncer colorrectal en población china (2), con una mayor agresividad del adenocarcinoma esofágico en población holandesa (26) y, del cáncer gástrico familiar, en Corea del Sur (20,27), resultados que indican la importancia de estudiar estos polimorfismos en diferentes poblaciones, pues la variabilidad genética puede influir en su efecto en la propensión individual a desarrollar cáncer.…”

Failure to detect significant association between estrogen receptor-alpha gene polymorphisms and endometriosis in Japanese women

“…Some studies observed a positive association between endometriosis and ESR1 polymorphisms and splicing variants [15][16][17], whereas others reported equivocal or negative results [10,19]. Polymorphisms and ER-related genotypes may also determine the function of the sex-steroid system both at the receptor level and at the level of hormone synthesis [24,25].…”

“…Some previous studies have reported on the existence of a positive association between endometriosis and ESR1 polymorphisms and splicing variants [15][16][17]. However, the results of other studies are inconsistent, cannot be replicated, and may vary because of differences between cohorts and populations, diagnostic errors, differences in sample sizes and in choice and type of genetic markers, and errors in laboratory methodology [5,18,19].…”