Homozygosity for alanine in the mitochondrial targeting sequence of superoxide dismutase and risk for severe alcoholic liver disease

Background & Aims: For similar ethanol consumption, some subjects only deve lop macrovacuolar steatosis whereas others develop severe liver lesions, A genetic dimorphism encodes for either alanine or valine in the mitochondria l targeting sequence of manganese superoxide dismutase and could modulate i ts mitochondrial import, Methods: The DNA of 71 white patients with alcohol ic liver disease and 79 white blood donors was amplified and genotyped, Res ults: The frequency of the alanine-encoding allele and the percentage of al anine homozygotes were higher in all patients than in controls and increase d with the severity of liver lesions, The percentage of alanine homozygotes was 19% in controls, 17% in alcoholic patients with macrovacuolar steatosi s, 43% in patients with microvesicular steatosis, 58% in patients with alco holic hepatitis, and 69% in patients with cirrhosis, Alcohol consumption in alcoholics was similar whatever the genotype, Alanine homozygosity did not change the risk of developing macrovacuolar steatosis in alcoholics, but i ncreased by 3-fold that of microvesicular steatosis, and 6- and 10-fold tha t of alcoholic hepatitis and cirrhosis, Conclusions: Homozygosity for alani ne in the mitochondrial targeting sequence of manganese superoxide does not modify alcohol consumption and the risk of macrovacuolar steatosis in alco holics but is a major risk factor for severe alcoholic liver disease.