Genetic variation in the microsomal triglyceride transfer protein (−493G/T) is associated with hepatic steatosis in patients infected with hepatitis C virus

Abstract

BackgroundIn chronic hepatitis C, the fibrosis progression rates are extremely variable and can be influenced by factors associated with the host, virus and environment. Among the associated metabolic factors, hepatic steatosis is characterized by an accumulation of triglycerides in hepatocytes. In the host, genetic determinants of hepatic steatosis are observed, such as single-nucleotide polymorphisms (SNPs) in the microsomal triglyceride transfer protein (MTTP) gene. The MTTP -493G/T SNP appears to play an important role in the regulation of gene expression and influences the plasma concentration of circulating low-density lipoprotein (LDL). The present study investigated the influence of this SNP in the development of hepatic steatosis in patients with chronic hepatitis C and evaluated the association of hepatic steatosis with certain characteristics of these patients and the hepatitis C virus (HCV).MethodsTwo hundred thirty-nine patients with chronic hepatitis C were genotyped for the MTTP -493G⁄T SNP by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The association between hepatic steatosis and selected characteristics of the patient and virus was evaluated using bivariate and multivariate analyses.ResultsThe most prevalent MTTP -493G/T genotype was GG (46%) followed by GT (43.5%) and TT (10.5%). Multivariate analysis of the total cohort revealed associations between the presence of hepatic steatosis and inflammatory activity of moderate to high intensity (P < 0.001), advanced age (P = 0.010), elevated gamma glutamyl transpeptidase (GGT) levels (P = 0.010) and low LDL levels (P = 0.022). Hepatic steatosis was also associated with the TT/GT genotype of the MTTP -493G⁄T SNP in patients infected with HCV genotype 3 (P < 0.001).ConclusionsIn chronic hepatitis C patients infected with HCV genotype 3 and with the TT/GT genotype of the MTTP -493G/T SNP, a significant increase in hepatic steatosis was observed, which may indicate that this SNP has a significant influence on the accumulation of triglycerides in hepatocytes. Furthermore, associations were observed between hepatic steatosis and inflammatory activity of moderate to high intensity, advanced age, elevated GGT and low LDL levels.

Antithyroid Drug Therapy for Graves’ Disease and Implications for Recurrence

“…In GD patients, the increased estradiol level is related to the positivity of TRAb [37]. Although the incidence of GD is higher in women, male GD patients have a higher risk of recurrence after ATD withdrawal [6, 34, 38, 39]. There are some possible explanations for the higher recurrence risk of male GD patients.…”

“…There are some possible explanations for the higher recurrence risk of male GD patients. First, male GD patients had larger goiter size, which was associated with severe immune and biochemical disorders [39]. Second, a family history of thyroid or nonthyroid autoimmune diseases occurred more frequently in male GD patients [39].…”

“…First, male GD patients had larger goiter size, which was associated with severe immune and biochemical disorders [39]. Second, a family history of thyroid or nonthyroid autoimmune diseases occurred more frequently in male GD patients [39]. So, the higher risk of recurrence in male GD patients might be associated with bigger goiter size and genetic background.…”

Alterações genéticas no gene MTTP e sua relação com níveis de lipídeos plasmáticos e esteatose hepática em pacientes com hepatite C crônica

“…Alguns SNPs no gene MTTP foram previamente associados com a esteatose hepática em pacientes com hepatite C crônica (Zampino et al, 2008;Mirandola et al, 2009;Magri et al, 2017) (Cai et al, 2011). Porém, dados relacionados ao SNP -164T/C em pacientes com hepatite C crônica ainda são bastante escassos na literatura.…”

“…No presente estudo, o SNP H297Q não foi significativamente associado à presença de esteatose hepática em pacientes com hepatite C crônica, mesmo quando foi analisado em conjunto com outras características. Esse resultado difere da associação encontrada dos SNPs -164T/C e -400A/T, no presente estudo, e do SNP -493G/T no gene MTTP, em outros estudos, com a presença da esteatose hepática na população com hepatite C(Zampino et al, 2008;Mirandola et al, 2009;Magri et al, 2017). Esses SNPs estão localizados no mesmo gene, mas cada um deles tem uma posição genética distinta e às vezes gera mudanças nos aminoácidos, que podem ou não influenciar diversas patologias como a esteatose hepática.O presente trabalho não pretende ser um estudo definitivo sobre identificar fatores genéticos relacionados com desenvolvimento de esteatose hepática associada à infecção crônica por HCV, tendo em vista que outras variantes genéticas relevantes no hospedeiro precisam ser testadas.…”