title: Monozygotic twins with NASH cirrhosis: cumulative effect of multiple single nucleotide polymorphisms?
abstract: Multiple genetic and environmental factors interact to determine an individual's predisposition to non-alcoholic fatty liver disease and its phenotypic characteristics. Association studies have found a number of alleles associated with the development of non-alcoholic steatohepatitis. Our aim was to investigate whether multiple risk-associated alleles may be present in affected monozygotic twins, indicating underlying genetic predisposition to non-alcoholic steatohepatitis. We determined the genotype of 14 candidate gene polymorphisms (at 11 unlinked loci) in a set of monozygotic twins who presented with cirrhosis within 18 months of each other. Genotyping revealed multiple single nucleotide polymorphisms at 9 independent loci in genes PNPLA3, APOC3, GCKR, TRIB1, LYPLAL1, PPP1R3B, COL13A1, and EFCAB4B, previously implicated in contributing to non-alcoholic steatohepatitis pathogenesis. In conclusion, this case series illustrates the potential cumulative effect of multiple polymorphisms in the development and potential progression of a complex trait such as NASH cirrhosis.
authors: NIHR Nottingham Digestive Diseases Biomedical Research Unit, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham NG7 2UH, UK.
authors: Jane I
authors: JI
authors: Grove
authors: Department of Gastroenterology and Hepatology, Brighton and Sussex University Hospital, Brighton, BN2 5BE, UK.
authors: Mark
authors: M
authors: Austin
authors: Department of Gastroenterology and Hepatology, Brighton and Sussex University Hospital, Brighton, BN2 5BE, UK.
authors: Jeremy
authors: J
authors: Tibble
authors: NIHR Nottingham Digestive Diseases Biomedical Research Unit, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham NG7 2UH, UK.
authors: Guruprasad P
authors: GP
authors: Aithal
authors: Department of Gastroenterology and Hepatology, Brighton and Sussex University Hospital, Brighton, BN2 5BE, UK; Department of Medicine, Brighton and Sussex Medical School, Brighton, BN1 9PX, UK.
authors: Sumita
authors: S
authors: Verma
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000368:Aged; D053305:Apolipoprotein C-III / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000235:genetics; D024181:Collagen Type XIII / Q000235:genetics; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008049:Lipase / Q000235:genetics; D008103:Liver Cirrhosis / Q000209:etiology / Q000235:genetics*; D008245:Lysophospholipase / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D054645:Protein Phosphatase 1 / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D014430:Twins, Monozygotic / Q000235:genetics*; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D053305:Apolipoprotein C-III; D002135:Calcium-Binding Proteins; D024181:Collagen Type XIII; D047908:Intracellular Signaling Peptides and Proteins; D008049:Lipase; D008245:Lysophospholipase; D008565:Membrane Proteins; D054645:Protein Phosphatase 1; D017346:Protein Serine-Threonine Kinases; C551025:CRACR2A protein, human; C485100:GCKR protein, human; C493170:TRIB1 protein, human; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent; C561408:LYPLAL1 protein, human; C586823:PPP1R3B protein, human