Heterozygosity for HFE gene mutations and alcohol abuse are additive risk factors for biochemical iron overload

Abstract

HETEROZYGOSITY FOR HFE GENE MUTATIONS AND ALCOHOL ABUSE ARE ADDITIVE RISK FACTORS FOR BIOCHEMICAL IRON OVERLOAD S. Moodie, L. Ang, J. Stenner, G.E. Levin, J.D Maxwell St Georges Hospital and Medical School, Tooting, London SW 17 ORE, UK. Not all patients homozygous for the C282Y mutation develop clinical haemochromatosis. A high alcohol intake may be an additional risk factor in the phenotypic expression of haemochromatosis. Aims: to investigate the relationship between HFE gene mutations (C282Y and H63D), non-fasting serum iron markers and past alcohol intake, in unselected patients with a variety of liver diseases. Methods: Genomic DNA was prepared from EDTA blood, DNA fiagments amplified by restriction fragment length analysis and HFE mutations determined in 323 patients attending a liver clinic from an ethnically mixed population. Alcohol intake was determined by a single observer, and serum iron markers using standard assays (data not available in all patients). A transferrin saturation (TFS)>60% was taken as a marker for oiochemieal iron overload'. Results: 1. A past alcohol intake of>30 units/week was associated with significantly higher serum iron markers (ferritin p 60% P value * Wild type genes, no alcohol abuse 2% (1/40) Heterozgotes, no alcohol abuse 2% (1166) p=l (NS) Wild type ~enes, alcohol abuse 11% (7/65) p=0.26 (NS) Heterozygote, alcohol abuse 24% (10/41) p=0.007 (* p values comparing with wild type genes, no alcohol abuse) Condusions: In our liver clinic population both the presence of I ~ E gene mutations and previous alcohol abuse were associated with raised serum iron markers. Heavy alcohol consumption and heterozygosity for HFE mutations appear to be additive risk factors for developing a transferrin saturation > 60%. [ c1,/o ]