Plasmatic higher levels of homocysteine in Non-alcoholic fatty liver disease (NAFLD)

Abstract

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a chronic liver disease, which includes a spectrum of hepatic pathology such as simple steatosis, steatohepatitis, fibrosis and cirrhosis. The increased serum levels of homocysteine (Hcy) may be associated with hepatic fat accumulation. Genetic mutations in the folate route may only mildly impair Hcy metabolism. The aim of this study was to investigate the relation between liver steatosis with plasma homocysteine level and MTHFR C677T and A1298C polymorphisms in Brazilian patients with NAFLD.MethodsThirty-five patients diagnosed with NAFLD by liver biopsy and forty-five healthy controls neither age nor sex matched were genotyped for C677T and A1298C MTHFR polymorphisms using PCR-RFLP and PCR-ASA, respectively, and Hcy was determined by HPLC. All patients were negative for markers of Wilson’s, hemochromatosis and autoimmune diseases. Their daily alcohol intake was less than 100 g/week. A set of metabolic and serum lipid markers were also measured at the time of liver biopsies.ResultsThe plasma Hcy level was higher in NAFLD patients compared to the control group (p = 0.0341). No statistical difference for genotypes 677C/T (p = 0.110) and 1298A/C (p = 0.343) in patients with NAFLD and control subjects was observed. The genotypes distribution was in Hardy-Weinberg equilibrium (677C/T p = 0.694 and 1298 A/C p = 0.188). The group of patients and controls showed a statistically significant difference (p < 0.001) for BMI and HOMA_IR, similarly to HDL cholesterol levels (p < 0,006), AST, ALT, γGT, AP and triglycerides levels (p < 0.001). A negative correlation was observed between levels of vitamin B12 and Hcy concentration (p = 0.005).ConclusionOur results indicate that plasma Hcy was higher in NAFLD than controls. The MTHFR C677T and A1298C polymorphisms did not differ significantly between groups, despite the 677TT homozygous frequency was higher in patients (17.14%) than in controls (677TT = 4.44%) (p > 0.05). The suggested genetic susceptibility to the MTHFR C677T and A1298C should be confirmed in large population based studies.

Betaine chemistry, roles, and potential use in liver disease

“…Insulin resistance, reflected as hyperinsulinemia, is positively correlated with elevated plasma homocysteine in NASH patients [64,65]. In addition, there is decreased mitochondrial function and altered structure in NASH [66,67].…”

Nutritional Epigenetics and the Prevention of Hepatocellular Carcinoma with Bioactive Food Constituents

“…Furthermore, it has been demonstrated that humans eating low-choline diets and/or having genetic polymorphisms in choline and one-carbon metabolism genes develop NAFLD (104,105) and have a greater susceptibility to HCC (106,107). Additionally, Kuo et al (108) and Huang et al (97) showed, respectively, a link between a low blood folate and betaine status and HCC in humans, and de Carvalho et al (109) reported a higher level of plasma homocysteine in patients with NAFLD. Extensive evidence has established also that epigenetic changes induced by one-carbon metabolism abnormalities are the major contributors to the development of HCC in humans and experimental animals (110)(111)(112)(113).…”

Effects of Turmeric on Homocysteine and Fetuin-A in Patients With Nonalcoholic Fatty Liver Disease: A Randomized Double-Blind Placebo-Controlled Study

“…Evidence shows that elevated plasma Hcy, as a risk factor for CVD, alters intracellular lipid metabolism and is associated with hepatic fat accumulation (22).…”