Analysis of Polymorphic Alleles of the Genes Encoding the Phase 1 and 2 Detoxication Enzymes in Patients with Endometriosis

In: Russian Journal of Genetics · 2003 · vol. 39(4) , pp. 427–430 · doi:10.1023/a:1023313932362 · W34156121
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Defective genotypes of phase 2 xenobiotic detoxification genes (GSTM1, NAT2, GSTT1) were significantly more frequent in endometriosis patients than controls, suggesting an association.

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This study examined polymorphisms in xenobiotic detoxification genes encoding phase 1 enzymes (CYP1A1, mEPHX1, CYP2E1) and phase 2 enzymes (NAT2, GSTM1, GSTT1) using PCR in 74 patients with extragenital endometriosis and compared their allele and genotype distributions to controls. The distributions of the listed phase 1 alleles and NAT2 and GSTM1 polymorphic alleles overall were reported to correspond to those in healthy individuals, but functionally defective genotypes GSTM1 0/0, NAT2 S/S; GSTM1 0/0, GSTT1 0/0; and GSTT1 0/0, NAT2 S/S were reported as three-, four-, and eight-times more frequent among patients than in healthy individuals. The authors discuss possible mechanisms for this association and suggest that NAT2, GSTM1, and GSTT1 genotyping could help assess predisposition to endometriosis, though no explicit limitation is stated in the provided text. This paper is centrally about endometriosis — it analyzes phase 1 and phase 2 detoxification enzyme gene polymorphisms and reports an increased frequency of specific defective phase 2 genotypes in extragenital endometriosis patients.

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Abstract

Polymorphysms of the three genes encoding phase 1 (CYP1A1, mEPHX1, and CYP2E1) and the three genes encoding phase 2 (NAT2, GSTM1, and GSTT1) xenobiotic detoxication enzymes were typed by use of PCR in 74 patients with extragenital endometriosis. Distribution of the CYP1A1, mEPHX1, CYP2E1, NAT2,and GSTM1polymorphic alleles in the patient group corresponded to that in the control group. At the same time, functionally defective genotypes GSTM1 0/0, NAT2 S/S; GSTM1 0/0, GSTT1 0/0; and GSTT1 0/0, NAT2 S/S were three, four, and eight times more frequent among the patients than in healthy individuals. This observation suggests the existence of a distinct association between the functionally defective alleles of the phase 2 xenobiotic detoxication and endometriosis. Possible mechanisms underlying this association are discussed. It is suggested that typing of the NAT2, GSTM1, and GSTT1 genes can be useful for the assessment of the predisposition to endometriosis. Similar content being viewed by others

References

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