Combined Effect of the PGR +331C > T, CYP17A1 -34A > G and CYP19A1 1531G > A Polymorphisms on the Risk of Developing Endometriosis

Jéssica Vilarinho Cardoso; Daniel Escorsim Machado; Renato Ferrari; Mayara Calixto da Silva; Plínio Tostes Berardo; Jamila Alessandra Perini

doi:10.1055/s-0037-1604097

Revista Brasileira de Ginecologia e Obstetrícia / RBGO Gynecology and Obstetrics, Table of Contents

CC BY-NC-ND 4.0 · Rev Bras Ginecol Obstet 2017; 39(06): 273-281
DOI: 10.1055/s-0037-1604097

Original Article

Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil

Combined Effect of the PGR +331C > T, CYP17A1 -34A > G and CYP19A1 1531G > A Polymorphisms on the Risk of Developing Endometriosis

Efeito combinado dos polimorfismos PGR +331C > T, CYP17A1 -34A > G e CYP19A1 1531G > A no risco de desenvolvimento da endometriose

Jéssica Vilarinho Cardoso

¹Research Laboratory of Pharmaceutical Sciences, Pharmacy Unit, Centro Universitário Estadual da Zona Oeste, Rio de Janeiro, Rio de Janeiro, Brazil

² Post-graduation in Public Health and Natural Environment Program, Escola Nacional de Saúde Pública Sergio Arouca, Fundação Oswaldo Cruz (National School of Public Health, Oswaldo Cruz Foundation), Rio de Janeiro, Rio de Janeiro, Brazil

,

Daniel Escorsim Machado

¹Research Laboratory of Pharmaceutical Sciences, Pharmacy Unit, Centro Universitário Estadual da Zona Oeste, Rio de Janeiro, Rio de Janeiro, Brazil

,

Renato Ferrari

³Gynecology Institute, Universidade Federal do Rio de Janeiro, Hospital Moncorvo Filho, Rio de Janeiro, Rio de Janeiro, Brazil

,

Mayara Calixto da Silva

¹Research Laboratory of Pharmaceutical Sciences, Pharmacy Unit, Centro Universitário Estadual da Zona Oeste, Rio de Janeiro, Rio de Janeiro, Brazil

,

Plínio Tostes Berardo

⁴Gynecology Service, Hospital Federal dos Servidores do Estado, Rio de Janeiro, Rio de Janeiro, Brazil

,

Jamila Alessandra Perini

¹Research Laboratory of Pharmaceutical Sciences, Pharmacy Unit, Centro Universitário Estadual da Zona Oeste, Rio de Janeiro, Rio de Janeiro, Brazil

² Post-graduation in Public Health and Natural Environment Program, Escola Nacional de Saúde Pública Sergio Arouca, Fundação Oswaldo Cruz (National School of Public Health, Oswaldo Cruz Foundation), Rio de Janeiro, Rio de Janeiro, Brazil

› Author Affiliations

Abstract

Purpose To evaluate the magnitude of the association of the polymorphisms of the genes PGR, CYP17A1 and CYP19A1 in the development of endometriosis.

Methods This is a retrospective case-control study involving 161 women with endometriosis (cases) and 179 controls. The polymorphisms were genotyped by real-time polymerase chain reaction using the TaqMan system. The association of the polymorphisms with endometriosis was evaluated using the multivariate logistic regression.

Results The endometriosis patients were significantly younger than the controls (36.0 ± 7.3 versus 38.0 ± 8.5 respectively, p = 0.023), and they had a lower body mass index (26.3 ± 4.8 versus 27.9 ± 5.7 respectively, p = 0.006), higher average duration of the menstrual flow (7.4 ± 4.9 versus 6.1 ± 4.4 days respectively, p = 0.03), and lower average time intervals between menstrual periods (25.2 ± 9.6 versus 27.5 ± 11.1 days respectively, p = 0.05). A higher prevalence of symptoms of dysmenorrhea, dyspareunia, chronic pelvic pain, infertility and intestinal or urinary changes was observed in the case group when compared with the control group. The interval between the onset of symptoms and the definitive diagnosis of endometriosis was 5.2 ± 6.9 years. When comparing both groups, significant differences were not observed in the allelic and genotypic frequencies of the polymorphisms PGR +331C > T, CYP17A1 -34A > G and CYP19A1 1531G > A, even when considering the symptoms, classification and stage of the endometriosis. The combined genotype PGR +331TT/CYP17A1 -34AA/CYP19A11531AA is positively associated with endometriosis (odds ratio [OR] = 1.72; 95% confidence interval [95%CI] = 1.09–2.72).

Conclusions The combined analysis of the polymorphisms PGR-CYP17A1-CYP19A1 suggests a gene-gene interaction in the susceptibility to endometriosis. These results may contribute to the identification of biomarkers for the diagnosis and/or prognosis of the disease and of possible molecular targets for individualized treatments.

Resumo

Objetivo Avaliar a magnitude de associação de polimorfismos nos genes PGR, CYP17A1 e CYP19A1 no desenvolvimento da endometriose.

Métodos Este é um estudo retrospectivo do tipo caso-controle, envolvendo 161 mulheres com endometriose (casos) e 179 controles. Os polimorfismos foram genotipados pela reação em cadeia da polimerase em tempo real utilizando o sistema TaqMan. A associação dos polimorfismos estudados com a endometriose foi avaliada pela regressão logística multivariada.

Resultados As pacientes com endometriose eram significativamente mais jovens do que os controles (36,0 ± 7,3 versus 38,0 ± 8,5, respectivamente, p = 0,023), apresentaram um índice de massa corporal menor (26,3 ± 4,8 versus 27,9 ± 5,7, respectivamente, p = 0,006), maior tempo médio de duração do fluxo menstrual (7,4 ± 4,9 versus 6,1 ± 4,4 dias, respectivamente, p = 0,03) e menor tempo médio do intervalo entre as menstruações (25,2 ± 9,6 versus 27,5 ± 11,1 dias, respectivamente, p = 0,05). Uma maior prevalência dos sintomas de dismenorreia, dispareunia, dor pélvica crônica, infertilidade, alterações intestinais e urinárias foi observada no grupo casos comparado ao grupo controle. O tempo médio entre o início dos sintomas e o diagnóstico definitivo de endometriose foi de 5,2 ± 6,9 anos. Comparando os dois grupos, não foram observadas diferenças significativas nas frequências alélicas e genotípicas dos polimorfismos PGR +331C > T, CYP17A1 -34A > G e CYP19A1 1531G > A, e nem considerando os sintomas, a classificação e o estadiamento da endometriose. O genótipo combinado PGR +331TT/CYP17A1 -34AA/CYP19A11531AA está associado positivamente com a endometriose (razão de possibilidades [RP] = 1,72; intervalo de confiança de 95% [IC95%] = 1,09–2,72).

Conclusões A análise combinada dos polimorfismos PGR-CYP17A1-CYP19A1 sugere uma interação gene-gene na susceptibilidade à endometriose. Estes resultados podem contribuir para a identificação de biomarcadores para o diagnóstico e/ou prognóstico da doença, assim como de possíveis alvos moleculares para um tratamento individualizado.

Keywords

polymorphisms - estrogens - endometriosis - biomarkers

Palavras-chave

polimorfismos - estrógenos - endometriose - biomarcadores

Full Text

References

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