ASSOCIATION OF POLYMORPHISM OF ACE (I/D) AND PPAR-G2 (PRO12ALA) GENES WITH THE DEVELOPMENT OF NONALCOHOLIC FATTY LIVER DISEASE IN PATIENTS WITH ARTERIAL HYPERTENSION AND OBESITY

Abstract

Objective – To study the association of polymorphism of ACE (I/D) and PPAR-g2 (Pro12Ala) genes with the onset of non-alcoholic steatohepatitis and steatohepatosis in patients suffering from essential arterial hypertension (EAH) and abdominal obesity (AO). Materials and methods. The prospective study involved 96 patients with non-alcoholic fatty liver disease (NAFLD), stage II EAH of 1-2 degrees of high and very high risk with concomitant AO. There were 41,67 % (40) of men and 58,33 % (56) women, the average age was 53,70±5,34 years. The function of the liver was studied by the activity of organspecific enzymes. The study of polymorphism of PPAR-g2 (Pro12Ala) and АСЕ (I/D) genes was carried out by using the PCR method. The control group consisted of 50 practically healthy individuals. Results. First degree obesity (OB) was diagnosed in 27,08 % (26) individuals, second degree OB was found in 58,33 % (56), 14,58 % (14) of patients had third degree OB; 16,67 % (16) individuals suffered from steatohepatitis with minimal activity of mesenchymal and inflammatory process, the rest 83,33 % (80) of the patients had steatohepatosis. Among the residents of the Northern Bukovyna suffering from NAFLD, OB and EAH the deletion in the 16th intron of the АСЕ (rs 4646994) gene in the homozygous condition occurs in 32,29 % of cases, which is by14,29 % more frequently than in the individuals of the control group (χ2=3.38; р=0,048). The unfavorable D-allele of the ACE gene is associated in patients with NAFLD and EAH with II and III degree obesity (χ2=5,24; р=0,022 and χ2=6,11; р=0.013, respectively) and occurs in general more frequently in patients by12,29 % (χ2=3,99; р=0,046). The DD genotype and D-allele are also associated with a higher incidence of steatohepatosis by 20,57 % (χ2=3,81; р=0,05) and 13,75 % (χ2=4,68; р=0,03), respectively. Frequency of homozygous missense mutation in chromosome 3 of codon 12 of exon B of PPAR-g2 (rs1801282) gene exists in 2,0 % of practically healthy individuals and in 5,21 % of patients with NAFLD, EAH and AO (р>0.05). In general, Pro-allele is prevalent among the examined individuals by 6.14 and 3.85 times (p<0,001), which is more common in the control than in patients with NAFLD, EAH and first degree AO by16.77% (χ2=5,06; р=0,024). Ala-allele, as well as AlaAla- and ProAla-genotypes are associated with a higher incidence of steatohepatitis by 30,25 % (χ2=4,99; р=0,025) and 17,25 % (χ2=4,85; р=0,028) respectively. Limitations of the study / consequences. The limitations are due to the lack of a puncture biopsy of the liver / consequences – the accuracy of diagnosis of NAFLD is based on clinical and laboratory findings and those of ultrasound examination. Novelty / value. This original study provides data allowing to assess the association of ACE (I/D) and PPAR-g2 (Pro12Ala) genes with NAFLD, EAH and AO considering the type of NAFLD and the degrees of obesity. Conclusions. In patients with Non-alcoholic Fatty Liver Disease, Essential Arterial Hypertension the unfavorable D-allele of the ACE (rs4646994) gene is associated with II and III obesity degree and higher incidence of steatohepatosis; Ala-allele of the PPAR-g2 (rs1801282) gene is associated with a higher incidence of steatohepatitis.