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Int. J. Mol. Sci. 2017, 18(12), 2560; https://doi.org/10.3390/ijms18122560

Estrogen Metabolism-Associated CYP2D6 and IL6-174G/C Polymorphisms in Schistosoma haematobium Infection

1
Department of Health Promotion and Chronic Diseases, National Institute of Health Dr. Ricardo Jorge (INSA), Rua Alexandre Herculano 321, 4000-055 Porto, Portugal
2
Department of Human Genetics, National Institute of Health Dr. Ricardo Jorge (INSA), Rua Alexandre Herculano 321, 4000-055 Porto, Portugal
3
Instituto de Ciências Biomédicas Abel Salazar (ICBAS/UP), Universidade do Porto, Rua Jorge Viterbo Ferreira 228, P 4050-313 Porto, Portugal
4
Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR/CIMAR), Universidade do Porto, Av. General Norton de Matos s/n, 4450-208 Matosinhos, Portugal
5
Division of Endocrinology, Diabetes and Metabolism, Santo Antonio Hospital—Centro Hospitalar do Porto (CHP), Largo do Prof. Abel Salazar, 4099-001 Porto, Portugal
6
Escola Superior de Saúde, Instituto Politécnico do Porto, Rua Dr. António Bernardino de Almeida, 400, 4200-079 Porto, Portugal
7
Unit of Metabolism, Nutrition and Endocrinology, Instituto de Investigação e Inovação da Universidade do Porto (i3S), Rua Alfredo Allen, 4200-135 Porto, Portugal
8
Departamento de Biomedicina, Unidade de Bioquímica, Faculdade de Medicina, Universidade do Porto, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
9
Institute of Tropical Medicine and International Health, Charité—Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
10
Fundação Professor Ernesto Morais, Rua de Monsanto 512, 4250-288 Porto, Portugal
*
Author to whom correspondence should be addressed.
Received: 2 October 2017 / Revised: 3 November 2017 / Accepted: 23 November 2017 / Published: 28 November 2017
(This article belongs to the Special Issue Molecular Pathways of Estrogen Receptor Action)
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Abstract

Schistosoma haematobium is a human blood fluke causing a chronic infection called urogenital schistosomiasis. Squamous cell carcinoma of the urinary bladder (SCC) constitutes chronic sequelae of this infection, and S. haematobium infection is accounted as a risk factor for this type of cancer. This infection is considered a neglected tropical disease and is endemic in numerous countries in Africa and the Middle East. Schistosome eggs produce catechol-estrogens. These estrogenic molecules are metabolized to active quinones that induce modifications in DNA. The cytochrome P450 (CYP) enzymes are a superfamily of mono-oxygenases involved in estrogen biosynthesis and metabolism, the generation of DNA damaging procarcinogens, and the response to anti-estrogen therapies. IL6 Interleukin-6 (IL-6) is a pleiotropic cytokine expressed in various tissues. This cytokine is largely expressed in the female urogenital tract as well as reproductive organs. Very high or very low levels of IL-6 are associated with estrogen metabolism imbalance. In the present study, we investigated the polymorphic variants in the CYP2D6 gene and the C-174G promoter polymorphism of the IL-6 gene on S. haematobium-infected children patients from Guine Bissau. CYP2D6 inactivated alleles (28.5%) and IL6G-174C (13.3%) variants were frequent in S. haematobium-infected patients when compared to previously studied healthy populations (4.5% and 0.05%, respectively). Here we discuss our recent findings on these polymorphisms and whether they can be predictive markers of schistosome infection and/or represent potential biomarkers for urogenital schistosomiasis associated bladder cancer and infertility. View Full-Text
Keywords: estrogen biosynthesis; estrogen metabolism; BMI; S. haematobium-associated bladder cancer estrogen biosynthesis; estrogen metabolism; BMI; S. haematobium-associated bladder cancer
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Cardoso, R.; Lacerda, P.C.; Costa, P.P.; Machado, A.; Carvalho, A.; Bordalo, A.; Fernandes, R.; Soares, R.; Richter, J.; Alves, H.; Botelho, M.C. Estrogen Metabolism-Associated CYP2D6 and IL6-174G/C Polymorphisms in Schistosoma haematobium Infection. Int. J. Mol. Sci. 2017, 18, 2560.

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