GENETIC-VARIANTS OF MICROSOMAL METABOLISM AND SUSCEPTIBILITY TO HYDROCARBON-ASSOCIATED GLOMERULONEPHRITIS

Hydrocarbon (HC) exposure can play a role in the development of chroni c glomerulonephritis (CN). Interindividual variations in various metab olizing enzymes may influence HC biotransformation, and hence suscepti bility to HC-associated CN. We evaluated the role of human genotypic p olymorphism in HC-associated CN, in 41 patients (30 male, 11 female) w ith primary CN (17 diffuse mesangial proliferative CN, 12 focal segmen tal CN, 11 membranous GN, one membranoproliferative CN) and 60 (46 mal e, 14 female) healthy controls. Genotypic polymorphisms of (CYP) P450 2D6 (CYP2D6), glutathione S-transferases mu (GSTM1) and theta (GSTT1) and N-acetyltransferase (NAT-2) were determined using polymerase chain reaction analysis of white-blood-cell DNA. HC exposure scores were de termined using a validated questionnaire, and were significantly eleva ted in CN patients compared to controls. While no significant differen ces in the various genotypic frequencies were observed in the CN group overall, compared to controls, there was a significant increase in GS TM1 null (n=10) to GSTM1 wild type (n=1), and NAT fast (n=10) to slow (n=1) acetylators, in the membranous GN group compared to controls (p <0.05). These results suggest a possible role for GSTM1 null and NAT f ast acetylator in the development of HC-associated membranous GN.