The Association of Nicotinamide Phosphoribosyltransferase Polymorphism with Markers of Hepatic Injury and De Novo Lipogenesis in Nonalcoholic Fatty Liver Disease

摘要

Background: De novo lipogenesis (DNL) increases in NAFLD and nicotinamide phosphoribosyltransferase (NAMPT) up regulates two essential enzymes in this pathway. On the other hand, NAMPT function could be affected by the promoter region polymorphism and sex hormones. Objectives: This study explored the association of -4689 G/T polymorphism in the promoter region of NAMPT gene with markers of hepatic injury and DNL in patients with NAFLD in order to see whether or not these associations are the same for both sexes. Methods: In this cross-sectional study, 62 consecutive patients (32 men and 30 women) with NAFLD were recruited. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to identify -4689 G/T polymorphism. DNL index of erythrocyte membrane as the marker of hepatic DNL was analyzed by gas chromatography. Fasting serum NAMPT, Caspase-cleaved cytokeratin 18 (cCK18), total soluble cytokeratin 18 (CK18), liver enzymes (AST, ALT, ALKP, GGT), and lipid-glucose profile were measured. Anthropometric measurements, Fibroscan, assessment of dietary intake and physical activity were also performed. Two-independent sample t test, chi-square test, one-way analysis of variance, and multiple linear regression were used to analyze the data. Results: Serum NAMPT and erythrocyte membrane DNL index were not significantly different among the three genotypes in both sexes. In men, serum AST (P = 0.04) and ALT (P = 0.03) were significantly higher in GT genotype than GG genotype. Serum CK18, cCK18, and CAP also had the highest levels in GT genotype but not statistically significant. In women, the markers of hepatic injury were not significantly different between GG and GT genotypes. Serum AST (P = 0.01), ALT (P = 0.01) and cCK18 (P = 0.001) levels were significantly higher in TT genotype. Serum GGT, CK18, and CAP also had the highest level in TT genotype but not statistically significant. These associations remained significant even after adjustment for confounding variables in multiple linear regression. Conclusions: -4689 G/T polymorphism was not associated with hepatic DNL index but T allele in this polymorphism was associated with increased biomarkers of hepatic inflammation, apoptosis and necrosis in patients with NAFLD especially in men, as one T allele (GT genotype) was enough for increased biomarkers of hepatic injury in men but not in women.