Molecular genetic markers and metabolic disorders in non-alcoholic fatty liver disease

Aim: to assess the probability of unfavorable outcomes of non-alcoholic fatty liver disease (NAFLD) based on clinical, biochemical, and molecular genetic parameters. Patients and Methods: 440 individuals were examined. Among them, 115 patients (84 men and 31 women) aged 23–69 (mean 49.3±1.1 years) were diagnosed with NAFLD and 325 healthy volunteers (172 men and 153 women) aged 25–67 (mean age 47.9±0.6 years) were controls. Molecular genetic testing for TCF7L2 (ТС, СС, and ТТ genotypes) was performed in all participants. The rates of Glu342Lys (PIZ) and Glu264Val (PIS) mutations of α1-antitrypsin gene (SERPINA1) and 282Y and 63D alleles of hemochromatosis (HFE) gene were evaluated. Standard liver function tests (ASAT, ALAT, bilirubin), lipid metabolism (total cholesterol, triglycerides, HDL, LDL), excretory porphyrin metabolism (porphyrin precursors [δ-aminolaevulinic acid and porphobilinogen] and fractions [uroporphyrin and coproporphyrin]), and cytokine profile (interleukins 1β, 6, 8, 10, and 1Ra, tumor necrosis factor/TNF α) were assessed. Results: the rates of TCF7L2 genotype, 282Y and 63D HFE gene alleles were similar in NAFLD patients and healthy controls. Meanwhile, Glu342Lys (PIZ) and Glu264Val (PIS) SERPINA1 gene polymorphisms were significantly more common in NAFLD patients vs. general population. The odds ratio (OR) has demonstrated that Glu342Lys (PIZ) genotype occurrence is 3.9 times greater in the NAFLD group than in healthy controls (NZ + ZZ vs. NN: OR=3.90, 95% CI 1.5–10.5, p=0.007), while Glu264Vol (PIS) genotype occurrence is 6.6 times greater in the NAFLD group than in healthy controls (NS vs. NN: OR=6.6, 95 CI 2.4–18.3, p<0.001). Abnormalities of porphyrin metabolism and cytokine profile were detected in most participants (71.3% and 82.6%, respectively). Unfavorable NAFLD outcomes were reported in 30 patients (26.1%). Conclusions: molecular genetic testing and specific blood biochemistry allows for predicting NAFLD outcome. Describing metabolic disorders allows for assessing the risk of unfavorable outcome. KEYWORDS: non-alcoholic fatty liver disease, molecular genetic testing, TCF7L2 gene, α1-antitrypsin gene (SERPINA1), hemochromatosis gene (HFE), lipid metabolism, porphyrin metabolism, cytokine profile, unfavorable outcome. FOR CITATION: Krivosheev A.B., Maksimov V.N., Boyko K.Yu. et al. Molecular genetic markers and metabolic disorders in non-alcoholic fatty liver disease. Russian Medical Inquiry. 2022;6(5):206–212 (in Russ.). DOI: 10.32364/2587-6821-2022-6-5-206-212.