Gastroenterology
Volume 136, Issue 5 , Pages 1585-1592 , May 2009

Heritability of Nonalcoholic Fatty Liver Disease

  • Jeffrey B. Schwimmer

      Affiliations

    • Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, San Diego, California
    • Department of Gastroenterology, Rady Children's Hospital San Diego, San Diego, California
    • Corresponding Author InformationReprint requests Address requests for reprints to: Jeffrey B. Schwimmer, MD, Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego, 200 West Arbor Drive, San Diego, California 92103. fax: (619) 543-7537
    • ,
  • Manuel A. Celedon

      Affiliations

    • Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, San Diego, California
    • ,
  • Joel E. Lavine

      Affiliations

    • Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, San Diego, California
    • Department of Gastroenterology, Rady Children's Hospital San Diego, San Diego, California
    • ,
  • Rany Salem

      Affiliations

    • Scripps Genomic Medicine and The Scripps Translational Sciences Institute, Scripps Health and The Scripps Research Institute, La Jolla, California
    • ,
  • Nzali Campbell

      Affiliations

    • Scripps Genomic Medicine and The Scripps Translational Sciences Institute, Scripps Health and The Scripps Research Institute, La Jolla, California
    • ,
  • Nicholas J. Schork

      Affiliations

    • Scripps Genomic Medicine and The Scripps Translational Sciences Institute, Scripps Health and The Scripps Research Institute, La Jolla, California
    • ,
  • Masoud Shiehmorteza

      Affiliations

    • Liver Imaging Group, Department of Radiology, University of California, San Diego School of Medicine, San Diego, California
    • ,
  • Takeshi Yokoo

      Affiliations

    • Liver Imaging Group, Department of Radiology, University of California, San Diego School of Medicine, San Diego, California
    • ,
  • Alyssa Chavez

      Affiliations

    • Liver Imaging Group, Department of Radiology, University of California, San Diego School of Medicine, San Diego, California
    • ,
  • Michael S. Middleton

      Affiliations

    • Liver Imaging Group, Department of Radiology, University of California, San Diego School of Medicine, San Diego, California
    • ,
  • Claude B. Sirlin

      Affiliations

    • Liver Imaging Group, Department of Radiology, University of California, San Diego School of Medicine, San Diego, California

Received 17 September 2008 ,Accepted 22 January 2009.

References 

  1. Schwimmer JB, Deutsch R, Kahen T, et al. Prevalence of fatty liver in children and adolescents. Pediatrics. 2006;118:1388–1393
  2. Beymer C, Kowdley KV, Larson A, et al. Prevalence and predictors of asymptomatic liver disease in patients undergoing gastric bypass surgery. Arch Surg. 2003;138:1240–1244
  3. Xanthakos S, Miles L, Bucuvalas J, et al. Histologic spectrum of nonalcoholic fatty liver disease in morbidly obese adolescents. Clin Gastroenterol Hepatol. 2006;4:226–232
  4. Kim HJ, Lee KE, Kim DJ, et al. Metabolic significance of nonalcoholic fatty liver disease in nonobese, nondiabetic adults. Arch Intern Med. 2004;164:2169–2175
  5. Nobili V, Marcellini M, Devito R, et al. NAFLD in children: a prospective clinical-pathological study and effect of lifestyle advice. Hepatology. 2006;44:458–465
  6. Struben VM, Hespenheide EE, Caldwell SH. Nonalcoholic steatohepatitis and cryptogenic cirrhosis within kindreds. Am J Med. 2000;108:9–13
  7. Willner IR, Waters B, Patil SR, et al. Ninety patients with nonalcoholic steatohepatitis: insulin resistance, familial tendency, and severity of disease. Am J Gastroenterol. 2001;96:2957–2961
  8. Browning JD, Szczepaniak LS, Dobbins R, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004;40:1387–1395
  9. Browning JD, Kumar KS, Saboorian MH, et al. Ethnic differences in the prevalence of cryptogenic cirrhosis. Am J Gastroenterol. 2004;99:292–298
  10. Szczepaniak LS, Nurenberg P, Leonard D, et al. Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population. Am J Physiol Endocrinol Metab. 2005;288:E462–E468
  11. Schwimmer JB, McGreal N, Deutsch R, et al. The influence of gender, race, and ethnicity on suspected fatty liver in obese adolescents. Pediatrics. 2005;115:e561–e565
  12. Louthan MV, Theriot JA, Zimmerman E, et al. Decreased prevalence of nonalcoholic fatty liver disease in black obese children. J Pediatr Gastroenterol Nutr. 2005;41:426–429
  13. Khoury MJ, Beaty TH, Cohen BH. Fundamentals of genetic epidemiology. New York: Oxford University Press; 1993;
  14. Vitzthum VJ. A number no greater than the sum of its parts: the use and abuse of heritability. Hum Biol. 2003;75:539–558
  15. Schwimmer JB, Behling C, Newbury R, et al. Histopathology of pediatric nonalcoholic fatty liver disease. Hepatology. 2005;42:641–648
  16. Brunt EM. Nonalcoholic steatohepatitis: definition and pathology. Semin Liver Dis. 2001;21:3–16
  17. Committee on Prevention of Obesity in Children and Youth. Preventing childhood obesity health in the balance. Washington, DC: The National Academies Press; 2005;
  18. Dixon WT. Simple proton spectroscopic imaging. Radiology. 1984;153:189–194
  19. Hussain HK, Chenevert TL, Londy FJ, et al. Hepatic fat fraction: MR imaging for quantitative measurement and display—early experience. Radiology. 2005;237:1048–1055
  20. Liu CY, McKenzie CA, Yu H, et al. Fat quantification with IDEAL gradient echo imaging: correction of bias from T(1) and noise. Magn Reson Med. 2007;58:354–364
  21. Bydder M, Yokoo T, Hamilton G, et al. Relaxation effects in the quantification of fat using gradient echo imaging. Magn Reson Imaging. 2008;26:347–359
  22. Yu H, McKenzie CA, Shimakawa A, et al. Multiecho reconstruction for simultaneous water-fat decomposition and T2* estimation. J Magn Reson Imaging. 2007;26:1153–1161
  23. Allison DB, Neale MC, Zannolli R, et al. Testing the robustness of the likelihood-ratio test in a variance-component quantitative-trait loci-mapping procedure. Am J Hum Genet. 1999;65:531–544
  24. Lange K, Little RJA, Taylor JMG. Robust statistical inference using the t distribution. J Am Stat Assoc. 1989;84:881–896
  25. Boehnke M, Lange K. Ascertainment and goodness of fit of variance component models for pedigree data. Prog Clin Biol Res. 1984;147:173–192
  26. Tokushige K, Yatsuji S, Hashimoto E, et al. Familial aggregation in patients with non-alcoholic steatohepatitis. Intern Med. 2008;47:405–410
  27. Abdelmalek MF, Liu C, Shuster J, et al. Familial aggregation of insulin resistance in first-degree relatives of patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2006;4:1162–1169
  28. Chitturi S, Farrell GC. Etiopathogenesis of nonalcoholic steatohepatitis. Semin Liver Dis. 2001;21:27–41
  29. Day CP. The potential role of genes in nonalcoholic fatty liver disease. Clin Liver Dis. 2004;8:673–691
  30. Shima Y, Tsukada T, Nakanishi K, et al. Association of Trp64Arg mutation of the B3-adrenergic receptor with fatty liver and mild glucose intolerance in Japanese subjects. Clin Chim Acta. 1998;274:167–176
  31. Iwamoto N, Ogawa Y, Kajihara S, et al. Gln27Glu beta2-adrenergic receptor variant is associated with hypertriglyceridemia and the development of fatty liver. Clin Chim Acta. 2001;314:85–91
  32. Valenti L, Fracanzani AL, Dongiovanni P, et al. Tumor necrosis factor alpha promoter polymorphisms and insulin resistance in nonalcoholic fatty liver disease. Gastroenterology. 2002;122:274–280
  33. Namikawa C, Shu-Ping Z, Vyselaar JR, et al. Polymorphisms of microsomal triglyceride transfer protein gene and manganese superoxide dismutase gene in non-alcoholic steatohepatitis. J Hepatol. 2004;40:781–786
  34. Nozaki Y, Saibara T, Nemoto Y, et al. Polymorphisms of interleukin-1B and B3-adrenergic receptor in Japanese patients with nonalcoholic steatohepatitis. Alcohol Clin Exp Res. 2004;28:106S–110S
  35. Song J, da Costa KA, Fischer LM, et al. Polymorphism of the PEMT gene and susceptibility to nonalcoholic fatty liver disease (NAFLD). FASEB J. 2005;19:1266–1271
  36. Brun P, Castagliuolo I, Floreani AR, et al. Increased risk of NASH in patients with the C(-159)T polymorphism in the CD14 gene promoter region. Gut. 2006;55:1212
  37. Westerbacka J, Kolak M, Kiviluoto T, et al. Genes involved in fatty acid partitioning and binding, lipolysis, monocyte/macrophage recruitment, and inflammation are overexpressed in the human fatty liver of insulin-resistant subjects. Diabetes. 2007;56:2759–2765
  38. Greco D, Kotronen A, Westerbacka J, et al. Gene expression in human NAFLD. Am J Physiol Gastrointest Liver Physiol. 2008;294:G1281–G1287
  39. Higuchi N, Kato M, Shundo Y, et al. Liver X receptor in cooperation with SREBP-1c is a major lipid synthesis regulator in nonalcoholic fatty liver disease. Hepatol Res. 2008;38:1122–1129

 Conflict of interest The authors disclose no conflicts.

 Funding This work was funded in part by grants from the National Institutes of Health including R21 DK71486 from the National Institute of Diabetes and Digestive and Kidney Diseases, P60 MD00220 for the San Diego EXPORT Center from the National Center of Minority Health and Health Disparities, and M01 RR000827 from the National Center for Research Resources for the General Clinical Research Center at University of California, San Diego, and grant DK080506 from the UCSD Digestive Diseases Research Development Center, San Diego. Dr Salem and Dr Schork are supported in part by Scripps Genomic Medicine and The Scripps Translational Sciences Institute.

PII: S0016-5085(09)00152-8

doi: 10.1053/j.gastro.2009.01.050

Gastroenterology
Volume 136, Issue 5 , Pages 1585-1592 , May 2009

Article Tools

* Image Usage & Resolution