title: Genetic variation in the microsomal triglyceride transfer protein (-493G/T) is associated with hepatic steatosis in patients infected with hepatitis C virus.
abstract: In 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).
  
  
  
  Two 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.
  
  
  
  The 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).
  
  
  
  In 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.
authors.affiliation: Laboratório de Investigação Médica em Hepatologia por Vírus (LIM-47), Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 470 - Instituto de Medicina Tropical - Prédio 2, 1º andar - sala 106. Bairro Cerqueira César, Sao Paulo, SP, CEP 05403-000, Brazil. mariana.magri@hc.fm.usp.br.
authors.forename: Mariana Cavalheiro
authors.initials: MC
authors.lastname: Magri
authors.affiliation: Laboratório de Investigação Médica em Hepatologia por Vírus (LIM-47), Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 470 - Instituto de Medicina Tropical - Prédio 2, 1º andar - sala 106. Bairro Cerqueira César, Sao Paulo, SP, CEP 05403-000, Brazil.
authors.forename: Thamiris Vaz Gago
authors.initials: TV
authors.lastname: Prata
authors.affiliation: Laboratório de Investigação Médica em Hepatologia por Vírus (LIM-47), Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 470 - Instituto de Medicina Tropical - Prédio 2, 1º andar - sala 106. Bairro Cerqueira César, Sao Paulo, SP, CEP 05403-000, Brazil.
authors.forename: Caroline
authors.initials: C
authors.lastname: Manchiero
authors.affiliation: Laboratório de Investigação Médica em Hepatologia por Vírus (LIM-47), Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 470 - Instituto de Medicina Tropical - Prédio 2, 1º andar - sala 106. Bairro Cerqueira César, Sao Paulo, SP, CEP 05403-000, Brazil.
authors.forename: Bianca Peixoto
authors.initials: BP
authors.lastname: Dantas
authors.affiliation: Departamento de Moléstias Infecciosas e Parasitárias, Hospital das Clínicas. Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, SP, Brazil.
authors.forename: Celso Carmo
authors.initials: CC
authors.lastname: Mazza
authors.affiliation: Laboratório de Investigação Médica em Hepatologia por Vírus (LIM-47), Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 470 - Instituto de Medicina Tropical - Prédio 2, 1º andar - sala 106. Bairro Cerqueira César, Sao Paulo, SP, CEP 05403-000, Brazil.|Departamento de Moléstias Infecciosas e Parasitárias, Hospital das Clínicas. Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, SP, Brazil.
authors.forename: Fátima Mitiko
authors.initials: FM
authors.lastname: Tengan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D054458:Amplified Fragment Length Polymorphism Analysis; D002352:Carrier Proteins / Q000235:genetics*; D005234:Fatty Liver / Q000175:diagnosis / Q000235:genetics* / Q000821:virology*; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies
chemical_list: D002352:Carrier Proteins; D005819:Genetic Markers; C106092:microsomal triglyceride transfer protein
keywords: Chronic hepatitis C; Hepatic steatosis; Microsomal triglyceride transfer protein (MTTP); Single nucleotide polymorphism (SNP)