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Q J Med 2001; 94: 79-87
© 2001 Association of Physicians

Membranous nephropathy, hydrocarbon exposure and genetic variants of hydrocarbon detoxification

C.W. Gradden, P. Pai, P. Hindell1, D.J. O'Donoghue2, H. Mason1 and G.M. Bell

From the Regional Renal Unit, Royal Liverpool Hospital, Liverpool, and 1 Health and Safety Laboratory, Broad Lane, Sheffield, 2 Department of Renal Medicine, Salford Royal Hospitals NHS Trust, Salford, Manchester, UK

Received 9 March 2000 and in revised form 8 November 2000

Modulation of biotransformation by genetic traits may be important in determining environmentally-induced nephrotoxicity. We conducted a case-control study to investigate the role of occupational hydrocarbon exposure, along with polymorphisms of the genes coding for N-acetyltransferase 2 (NAT2) and glutathione S-transferase µ (GSTµ), in the development of idiopathic membranous glomerulonephritis (IMGN). Patients (n=36) with biopsy-proven IMGN were matched with healthy controls for age, gender, and geographical area. Lifetime hydrocarbon exposure was assessed by a validated questionnaire. The polymorphisms of the NAT2 and GSTµ genes (GSTM1) were defined by use of a polymerase chain reaction on white-cell DNA from peripheral blood. Exposure to hydrocarbons was significantly greater in patients with IMGN than in controls (mean±SEM hydrocarbon exposure score 11 003±2955.7 vs. 4352±1418, p<0.02). NAT2 acetylator status was identical in patients and controls with 23 (63.9%) fast and 13 (36.1%) slow acetylators in each group. GSTµ was present in 15 (41.7%) patients and 16 (44.4%) controls. While occupational exposure to hydrocarbons remains a likely factor in its pathogenesis, further work is required to identify the genetic polymorphisms that modulate the risk of IMGN.

Address correspondence to Dr C. Gradden, Renal Unit, 6C Link, Royal Liverpool University Hospital Trust, Prescot Street, Liverpool L7 8XP. e-mail: farndon{at}freeuk.com


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