Possible involvement of arylamine N-acetyltransferase 2, glutathione S-transferases M1 and T1 genes in the development of endometriosis

Abstract

Wide inter-individual variation of expression of compound metabolic enzymes is determined by polymorphism and may predispose the development of diseases provoked by environmental factors. The combined analysis of phase II detoxification system genes: arylamine N-acetyltransferase 2 (NAT2), and glutathione S-transferases (GST) M1 and T1 was carried out in patients with minimal/mild (group I; n = 36) and moderate/severe endometriosis (group II; n = 29) and controls (n = 72) of French origin, using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The results show a significant difference between patients and controls with regard to NAT2 gene polymorphism (P < 0.05). This is mainly due to the high percentage of slow acetylator genotypes (SA) in patients compared with controls (60.0 versus 38.9%; P < 0.02) with a distinct preponderance in subjects with minimal/mild endometriosis (69.4%, P < 0.005) where there is a significantly elevated frequency of slow allele S1 (NAT2*5) (P = 0.05). Significantly increased proportions of GSTM1-deficient genotypes were found in both groups of patients, in comparison with the controls (75.0 and 79.3% versus 45.8%; P < 0. 0001). A preponderance of GSTT1-negative subjects among patients was also detected, but did not appear significant. We suggest the involvement of both NAT2 and GSTM1 detoxification system genes in the pathogenesis of endometriosis and the possible impact of NAT2 gene polymorphism in the development of different forms of this disease.

Endometriosis and the neoplastic process

“…iii) Inherited genetic polymorphisms in oestrogen and progesterone receptors (PRs), which predispose to endometriosis (Kitawaki et al 2001, Wieser et al 2002. iv) Inherited genetic polymorphisms in drug-metabolising enzymes (CYP1A1, CYP19 and GSTM1) which predispose to endometriosis (Baranova et al 1999, Hadfield et al 2001, Nakago et al 2001, Arvanitis et al 2003 and ovarian endometrioid and clear-cell cancers (Baxter et al 2001). These alterations may induce endometriosis or cancer by altering a dioxininduced oestrogen growth signal.…”

Biomarcadores de suscetibilidade à endometriose

“…Em nosso estudo, freqüências similares foram observadas para estes genótipos (44% para GSTM1 e 16% para GSTT1). Baranova et al 12 relataram alta freqüência do genótipo nulo GSTM1 em mulheres francesas com endometriose em relação ao controle (76,9 vs 45,8%) e concluíram que este genótipo representa fator de predisposição para endometriose. Outros autores também têm correlacionado o genótipo nulo GSTM1 com o desenvolvimento da endometriose e menos freqüentemente com o GSTT1 9,12,13 .…”

“…Desse modo, diferenças genéticas na regulação, expressão e atividade dos genes de fases I e II podem ser o fator crucial na suscetibilidade a certos tipos de doenças 7 . Realmente, polimorfismos em genes do biometabolismo têm sido identificados em inúmeras populações 7 e relacionados com neoplasias de pulmão 10 , fibrose cística 11 , bronquite crônica 8 e endometriose 9,12,13 .…”

Role of the Genetic Factors, Detoxication Systems and Oxidative Stress in the Pathogenesis of Endometriosis and Infertility (Review)

“…прошлого столетия было показано, что недостаточность системы детоксикации, предопределен-ная генетически, может стать фактором риска развития эндометриоза. Доказано, что ген глутатион S-трансферазы М 1 (GST), связанный со второй фазой детоксикации, играет существенную роль в патогенезе данного заболева-ния [17]. Более современные исследования с использова-нием резус-макак также позволили установить роль поли-морфизма гена ариламин N-ацетилтрансферазы (NAT2) в развитии эндометриоза [18].…”