Genetic and metabolic markers in the progression of nonalcoholic fatty liver disease in children

Abstract

Objective — to study the relationship of the NR1H4 gene polymorphisms and metabolic markers of the blood serum and bile acids in bile.Materials and methods. The observations, involving 55 children aged 10 to 17, have been performed at the Institute «Gastroenterology of the National Academy of Medical Sciences of Ukraine». The children were divided into two groups: the group 1 included patients with non‑alcoholic fatty liver disease (NAFLD) (n = 40); comparison group 2 consisted from children without NAFLD (n = 15). The investigation methods included PCR, biochemical, chromatographic analyses, and ELISA method.Results. As a result of the study, associations of NR1H4 gene genotypes (SNP rs11110390 (C/T)) with dyslipidemia, indicators of carbohydrate metabolism in children with NAFLD were revealed. The NR1H4 gene variability had a clear correlation with the increased probability of the NAFLD development in children. Dyslipidemia, which develops in children with the TT genotype, is characterized by the raised atherogenic coefficient and the decreased serum levels of HDL, that play the protective role. An imbalance in the bile acids’ levels in bile was observed.Conclusions. It has been established that carrier of the polymorphic variant SNP rs11110390 (C/T) of the NR1H4 gene in the homozygous state was associated with an increased probability of developing NAFLD in children. The changes in the lipid profile were detected with the «wild» genotype NR1H4 and in the homozygous state (TT). The increased levels of insulin, HOMA‑IR index in children with NAFLD can testify the development of insulin resistance as a factor in the formation of hepatic steatosis. An imbalance has been revealed in the levels of bile acids in portions B and C in the form of increased cholic acid levels of in the gallbladder bile and decreased levels in the liver.