Genetic predisposition to alcoholic toxic cirrhosis

Comprehensive analysis of the contribution of genetic factors into predispo sition to alcoholic toxic cirrhosis (TC) was performed. The ABO, RH, HP, TF , GC, PI, ACP1, PGM1, ESD, GLO1, and GST1 genetic polymorphisms were compar ed in 34- to 59-year-old male TC patients and control donors of the same se x and age. The phenotypic frequencies in the TC group deviated from the the oretically expected values; the main difference was the excess of rare homo zygotes for the loci GC, ACP1, ESD, and GLO1 In the TC patients, the observ ed heterozygosity (H-o) was considerably lower than the theoretically expec ted value (H-e). Wright's fixation index (F) in the TC patients was 30 time s higher than in the control group (0.0888 and 0.0027, respectively). A con siderable decrease in the ABO*0 allele frequency at the expense of an incre ase in the ABO*A allele frequency was observed in the TC patients as compar ed to the control sample. The TF*C2 allele frequency was two times higher i n the patients than in the control group (0.2571 and 0.1308, respectively). The frequencies of PI*Z and PI*S, the PI alleles that are responsible for lower concentrations of proteinase inhibitor, were 12 and 6 times higher in the TC than in the control group, The TC patients exhibited a significantl y higher frequency of the liver glutathione-S-transferase GST1*0 allele, wh ereas the GST1*2 frequency was two times higher in the control subjects tha n in the TC patients (0.2522 and 0.0953, respectively). The TC and control groups showed statistically significant differences in the frequencies of t he following alleles of six independent loci: ABO*0, TF*C1, TF*C2, P1*M1, P I*Z ACP1*C, PGM1*1+, PGM1*1-, PGM1*2-, GST1*0, and GST1*2. The haptoglobin level was significantly higher and the serum transferrin level was drastica lly lower in all phenotypic groups of TC patients than in control subjects. The concentrations of IgM and IgG depended on the HP, GC, and PI phenotype s. The total and direct reacting bilirubin concentrations depended on the r ed cell-enzyme phenotypes (ACP1, PGM1, and GLO1) in both TC and control gro ups.