Genetic polymorphisms in non-alcoholic fatty liver disease in obese Egyptian children

Abstract

Background/Aim:Polymorphisms in the promoter of microsomal triglyceride transfer protein (MTP) lead to decreased MTP transcription, less export of triglyceride from hepatocytes, and greater intracellular triglyceride accumulation. Therefore, functional polymorphisms in MTP may be involved in determining susceptibility to nonalcoholic steatohepatitis (NASH). The aim of this study is to examine the effect of some genetic influences among a group of obese Egyptian children.Patients and Methods:A cross-sectional study was conducted on 76 overweight and obese children presenting to the Pediatric Endocrinology Unit, Cairo University Children's Hospital, Egypt, as well as on 20 healthy controls. Anthropometric measurements were taken for all the patients and they underwent clinical examination, ultrasonographic examination of the liver, and liver biopsy when appropriate. Liver functions, blood glucose, serum insulin, C-peptide, and lipid profile were assessed and HOMA-IR calculated. Blood samples from biopsy-proven NASH patients and controls were analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism for the –493 G/T polymorphism in the promoter of MTP and the 1183 T/C polymorphism in the mitochondrial targeting sequence of manganese superoxide dismutase (MnSOD).Results:Eight had biopsy-proven simple steatosis and 7 had NASH. NASH patients had a much higher incidence of the MTP G/G genotype (P = 0.002, CI: 2.9–392) compared with the controls. NASH patients also had a 100% prevalence of the MnSOD T/T genotype.Conclusion:Certain genotypes in MTP and MnSOD are significantly more prevalent among obese children with NASH and may be responsible for such a phenotype.

Genetic variations of superoxide dismutase 2 and cytochrome P450 2E1 in non‐alcoholic steatohepatitis

“…In addition to environmental factors, genetic factors may have an important role in the development of NASH (4). Among these genetic factors, SOD2 is essential in hepatic lipid peroxidation and detoxification of many substances and toxins (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). We found that the SOD2 C variant was associated with increased risk of NASH.…”

“…Among the genetic variants of SOD2, the most important and best understood is 47T>C (rs4880) (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). The T to C substitution at position 47 in SOD2 results in an alanine for valine substitution in the leader amino acid sequence.…”

“…A Japanese study of NAFLD reported a higher incidence of the SOD2 T/T genotype in NASH patients (14). An Egyptian study also found that the SOD2 T/T genotype is associated with NASH incidence (15). A third study, which was conducted in the UK and Italy, found that individuals with the SOD2 T allele have a higher risk of more advanced fibrosis in NASH (16).…”

Correlation between MTP -493G>T polymorphism and non-alcoholic fatty liver disease risk: a meta-analysis

“…We reviewed the titles and abstracts of all articles and excluded 20 articles; full-texts and data integrity were also reviewed, and 16 additional articles were excluded. Finally, 11 case-control studies that met all of the inclusion criteria were included in this meta-analysis (Namikawa et al, 2004;Petit et al, 2006;Gambino et al, 2007;Zampino et al, 2008;Mirandola et al, 2009;Carulli et al, 2009;Oliveira et al, 2010;Musso et al, 2007Musso et al, , 2010El-Koofy et al, 2011;Siqueira et al, 2012). Publication years ranged from 2004-2012.…”

“…The MTP -493G>T polymorphism results from a G>T substitution in the intron region of NM_000253.2. Several previous studies have suggested that the MTP -493G>T polymorphism plays critical roles in the pathogenesis of NAFLD (Namikawa et al, 2004;Musso et al, 2007;Gambino et al, 2007;Zampino et al, 2008;Mirandola et al, 2009;Oliveira et al, 2010;Musso et al, 2010;El-Koofy et al, 2011;Siqueira et al, 2012).…”