Membranous nephropathy, hydrocarbon exposure and genetic variants of hydrocarbon detoxification.
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 mu (GSTmu), 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 GSTmu 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. GSTmu 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.
Gradden
C W
CW
Regional Renal Unit, Royal Liverpool Hospital, Liverpool, UK. farndon@freeuk.com
Pai
P
P
Hindell
P
P
O'Donoghue
D J
DJ
Mason
H
H
Bell
G M
GM
D001191:Arylamine N-Acetyltransferase / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000139:chemically induced* / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006018:Glycols / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D006838:Hydrocarbons / Q000009:adverse effects* / Q000378:metabolism / Q000494:pharmacology; D006840:Hydrocarbons, Alicyclic / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology; D006841:Hydrocarbons, Aromatic / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology; D006846:Hydrocarbons, Halogenated / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D016273:Occupational Exposure / Q000009:adverse effects*; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D012307:Risk Factors
D001191:Arylamine N-Acetyltransferase; D005982:Glutathione Transferase; D006018:Glycols; D006838:Hydrocarbons; D006840:Hydrocarbons, Alicyclic; D006841:Hydrocarbons, Aromatic; D006846:Hydrocarbons, Halogenated; C478900:NAT2 protein, human