Investigation of 2548G˃A leptine gene polymorphic variant impact on risk of non-alcoholic fatty liver disease in patients with type 2 diabettes mellitus

Abstract

Background. It is known that single nucleotide polymorphisms (SNPs) in adipokine genes can influence the development of pathological conditions associated with obesity, type 2 diabetes mellitus (T2D), non-alcoholic fatty liver disease (NAFLD) and their complications. In this study, we aimed to investigate the link between common -2548G > A (rs7799039) promoter variant of the human leptin gene (LEP) with leptin levels in type 2 diabetes patients with non-alcoholic fatty liver diseasese. Materials and methods. 61 patients with T2D aged from 28 to 80 years old (34 men / 27 women, age 56.40 ± 0.62 yrs, diabetes duration 7.72 ± 0.45 yrs, BMI 32.20 ± 0.43 kg/m2, WHR 1,00 ± 0,01, HbA1c 7.80 ± 0.19 %) with varying degrees of glycemic control and overweight, without renal insufficiency and 51 sex and age-match control subjects were examined. Genotyping according to SNP LEP 2548G > A was performed using the polymerase chain reaction method with appropriate primers and HhaI endonuclease. Results. In our study of T2DM patients with NAFLD compared to T2D patients without NAFLD features of dyslipidemia i.e. significant increase in triglycerides (p < 0,001), LDL cholesterol (p < 0,1), lower HDL cholesterol (p < 0.001) were found. Stratification of the diabetic patients in the presence and absence of NAFLD showed more pronounced increase in circulating leptin levels in the presence of NAFLD (84.73 ± 13.80 vs. 52.57 ± 6.86 μg/L, respectively), (p < 0.01), which justifies the feasibility of using this indicator for further needs as a diagnostic parameter of the above complication. In our study in GG carriers genotype of the G2548A LEP gene polymorphic locus type 2 diabetes patients with NAFLD the highest level of leptin was observed (159.15 μg/L), compared to other genotypes. Thus, it can be assumed that the G allele is associated with increased leptin levels in the blood of patients with NAFLD. This study showed that women with type 2 diabetes mellitus carrying the GG genotype with the G-2458A polymorphic variant of the LEP gene have 3.4 times higher leptin levels than men carrying the same genotype (p < 0.03). Conclusions. The data obtained regarding the 2548G > A polymorphic variant of the LEP gene can be used as a basis for personalized prevention and the formation of risk groups for the development of NAFLD