Meta-analysis of the influence of TM6SF2 E167K variant on Plasma Concentration of Aminotransferases across different Populations and Diverse Liver Phenotypes

Scientific Reports

Volumn 6, Issue , 2016, Pages

  Sookoian, Silvia ^a   Pirola, Carlos J ^a  

^a INSTITUTO DE INVESTIGACIONES MÉDICAS ALFREDO LANARI   (Argentina)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE AMINOTRANSFERASE; ASPARTATE AMINOTRANSFERASE; MEMBRANE PROTEIN; TM6SF2 PROTEIN, HUMAN;

ADULT; AGED; BLOOD; ENZYMOLOGY; FEMALE; GENE LINKAGE DISEQUILIBRIUM; GENETICS; HUMAN; MALE; META ANALYSIS; MIDDLE AGED; MISSENSE MUTATION; NONALCOHOLIC FATTY LIVER; VIRUS HEPATITIS;

ADULT; AGED; ALANINE TRANSAMINASE; ASPARTATE AMINOTRANSFERASES; FEMALE; HEPATITIS, VIRAL, HUMAN; HUMANS; LINKAGE DISEQUILIBRIUM; MALE; MEMBRANE PROTEINS; MIDDLE AGED; MUTATION, MISSENSE; NON-ALCOHOLIC FATTY LIVER DISEASE;

EID: 84973595088     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/srep27718     Document Type: Article

References (40)

1. Sherman, K. E. Alanine aminotransferase in clinical practice. A review. Arch. Intern. Med. 151, 260-265 (1991).
2. Sookoian, S. & Pirola, C. J. Alanine and aspartate aminotransferase and glutamine-cycling pathway: their roles in pathogenesis of metabolic syndrome. World J. Gastroenterol. 18, 3775-3781 (2012).
3. Goessling, W. et al. Aminotransferase levels and 20-year risk of metabolic syndrome, diabetes, and cardiovascular disease. Gastroenterology 135, 1935-1944 (2008).
4. Sookoian, S. et al. Serum aminotransferases in nonalcoholic fatty liver disease are a signature of liver metabolic perturbations at the amino acid and Krebs cycle level. Am. J. Clin. Nutr. 103, 422-434 (2016).
5. Illig, T. et al. A genome-wide perspective of genetic variation in human metabolism. Nat. Genet. 42, 137-141 (2010).
6. Shin, S. Y. et al. An atlas of genetic influences on human blood metabolites. Nat. Genet. 46, 543-550 (2014).
7. Bathum, L. et al. Evidence for a substantial genetic influence on biochemical liver function tests: results from a population-based Danish twin study. Clin. Chem. 47, 81-87 (2001).
8. Yuan, X. et al. Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes. Am. J. Hum. Genet. 83, 520-528 (2008).
9. Chambers, J. C. et al. Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma. Nat. Genet. 43, 1131-1138 (2011).
10. Romeo, S. et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat. Genet. 40, 1461-1465 (2008).
11. Sookoian, S. & Pirola, C. J. Meta-analysis of the influence of I148M variant of patatin-like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease. Hepatology 53, 1883-1894 (2011).
12. Kozlitina, J. et al. Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease. Nat. Genet. 46, 352-356 (2014).
13. Holmen,O. L. et al. Systematic evaluation of coding variation identifies a candidate causal variant in TM6SF2 influencing total cholesterol and myocardial infarction risk. Nat. Genet. 46, 345-351 (2014).
14. Pirola, C. J. & Sookoian, S. The dual and opposite role of the TM6SF2-rs58542926 variant in protecting against cardiovascular disease and conferring risk for nonalcoholic fatty liver: A meta-analysis. Hepatology 62, 1742-1756 (2015).
15. Coppola, N. et al. TM6SF2 E167K variant is associated with severe steatosis in chronic hepatitis C, regardless of PNPLA3 polymorphism. Liver Int. 35, 1959-1963 (2015).
16. Eslam, M. et al. Diverse impacts of the rs58542926 E167K variant in TM6SF2 on viral and metabolic liver disease phenotypes. Hepatology (2016). [Epub ahead of print].
17. Milano, M. et al. Transmembrane 6 superfamily member 2 gene E167K variant impacts on steatosis and liver damage in chronic hepatitis C patients. Hepatology 62, 111-117 (2015).
18. Petta, S. et al. TM6SF2 rs58542926 is not associated with steatosis and fibrosis in large cohort of patients with genotype 1 chronic hepatitis C. Liver Int. 36, 198-204 (2016).
19. Dongiovanni, P. et al. Transmembrane 6 superfamily member 2 gene variant disentangles nonalcoholic steatohepatitis from cardiovascular disease. Hepatology 61, 506-514 (2015).
20. Goffredo, M. et al. Role of TM6SF2 rs58542926 in the pathogenesis of nonalcoholic pediatric fatty liver disease: A multiethnic study. Hepatology 63, 117-125 (2016).
21. Grandone, A. et al. TM6SF2 Glu167Lys polymorphism is associated with low levels of LDL-cholesterol and increased liver injury in obese children. Pediatr. Obes. 11, 115-119 (2016).
22. Krawczyk, M., Stachowska, E., Milkiewicz, P., Lammert, F. & Milkiewicz, M. Reduction of Caloric Intake Might Override the Prosteatotic Effects of the PNPLA3 p.I148M and TM6SF2 p.E167K Variants in Patients with Fatty Liver: Ultrasound-Based Prospective Study. Digestion 93, 139-148 (2016).
23. Scorletti, E. et al. Treating liver fat and serum triglyceride levels in NAFLD, effects of PNPLA3 and TM6SF2 genotypes: Results from the WELCOME trial. J. Hepatol. 63, 1476-1483 (2015).
24. Sookoian, S. et al. Genetic variation in transmembrane 6 superfamily member 2 and the risk of nonalcoholic fatty liver disease and histological disease severity. Hepatology 61, 515-525 (2015).
25. Viitasalo, A. et al. Associations of TM6SF2 167K allele with liver enzymes and lipid profile in children: The PANIC Study. Pediatr. Res. (2016). [Epub ahead of print].
26. Wong, V. W., Wong, G. L., Tse, C. H. & Chan, H. L. Prevalence of the TM6SF2 variant and non-alcoholic fatty liver disease in Chinese. J. Hepatol. 61, 708-709 (2014).
27. Zhou, Y. et al. Circulating triacylglycerol signatures and insulin sensitivity in NAFLD associated with the E167K variant in TM6SF2. J. Hepatol. 62, 657-663 (2015).
28. Mencin, A. A. & Lavine, J. E. Advances in pediatric nonalcoholic fatty liver disease. Pediatr. Clin. North Am. 58, 1375-92, x (2011).
29. Kechagias, S. et al. Fast-food-based hyper-alimentation can induce rapid and profound elevation of serum alanine aminotransferase in healthy subjects. Gut 57, 649-654 (2008).
30. Maximos, M. et al. The role of liver fat and insulin resistance as determinants of plasma aminotransferase elevation in nonalcoholic fatty liver disease. Hepatology 61, 153-160 (2015).
31. Mofrad, P. et al. Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. Hepatology 37, 1286-1292 (2003).
32. Liu, R., Pan, X. & Whitington, P. F. Increased hepatic expression is a major determinant of serum alanine aminotransferase elevation in mice with nonalcoholic steatohepatitis. Liver Int. 29, 337-343 (2009).
33. Ioannou, G. N., Boyko, E. J. & Lee, S. P. The prevalence and predictors of elevated serum aminotransferase activity in the United States in 1999-2002. Am. J. Gastroenterol. 101, 76-82 (2006).
34. Ruhl, C. E. & Everhart, J. E. Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States. Gastroenterology 124, 71-79 (2003).
35. Hyun, H. J. et al. The prevalence of elevated alanine transaminase and its possible causes in the general Korean population. J. Clin. Gastroenterol. 48, 534-539 (2014).
36. Park, J. H., Kim, S. H., Park, S. & Park, M. J. Alanine aminotransferase and metabolic syndrome in adolescents: the Korean National Health and Nutrition Examination Survey Study. Pediatr. Obes. 9, 411-418 (2014).
37. Mahdessian, H. et al. TM6SF2 is a regulator of liver fat metabolism influencing triglyceride secretion and hepatic lipid droplet content. Proc. Natl. Acad. Sci. USA 111, 8913-8918 (2014).
38. Fan, Y. et al. Hepatic Transmembrane 6 Superfamily Member 2 Regulates Cholesterol Metabolism in Mice. Gastroenterology (2016). [Epub ahead of print].
39. Walker, E., Hernandez, A. V. & Kattan, M. W. Meta-analysis: Its strengths and limitations. Cleve. Clin. J. Med. 75, 431-439 (2008).
40. Begg, C. B. & Mazumdar, M. Operating characteristics of a rank correlation test for publication bias. Biometrics 50, 1088-1101 (1994).