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Cholesterol
Volume 2013 (2013), Article ID 298421, 10 pages
http://dx.doi.org/10.1155/2013/298421
Review Article

Current Views on Genetics and Epigenetics of Cholesterol Gallstone Disease

1Division of Internal Medicine Hospital of Bisceglie, 76011 Bisceglie, Italy
2Saint Louis University School of Medicine, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Edward Doisy Research Center, St. Louis, MO 63104, USA
3Clinica Medica “A. Murri”, Department of Biomedical Sciences & Human Oncology, University “Aldo Moro“ of Bari Medical School, 70124 Bari, Italy
4European Society for Clinical Investigation (ESCI), 3584 CJ Utrecht, The Netherlands

Received 28 January 2013; Revised 6 March 2013; Accepted 20 March 2013

Academic Editor: Gloria L. Vega

Copyright © 2013 Agostino Di Ciaula et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. E. Everhart and C. E. Ruhl, “Burden of digestive diseases in the united states part I: overall and upper gastrointestinal diseases,” Gastroenterology, vol. 136, no. 2, pp. 376–386, 2009. View at Publisher · View at Google Scholar · View at Scopus
  2. E. A. Shaffer, “Epidemiology and risk factors for gallstone disease: has the paradigm changed in the 21st century?” Current Gastroenterology Reports, vol. 7, no. 2, pp. 132–140, 2005. View at Scopus
  3. A. F. Attili, R. Capocaccia, N. Carulli et al., “Factors associated with gallstone disease in the MICOL experience,” Hepatology, vol. 26, no. 4, pp. 809–818, 1997. View at Scopus
  4. A. F. Attili, N. Carulli, E. Roda et al., “Epidemiology of gallstone disease in Italy: prevalence data of the multicenter Italian study on cholelithiasis (M.I.COL.),” The American Journal of Epidemiology, vol. 141, no. 2, pp. 158–165, 1995. View at Scopus
  5. A. K. Diehl, “Epidemiology and natural history of gallstone disease,” Gastroenterology Clinics of North America, vol. 20, no. 1, pp. 1–19, 1991. View at Scopus
  6. P. Portincasa and D. Q. Wang, “Intestinal absorption, hepatic synthesis, and biliary secretion of cholesterol: where are we for cholesterol gallstone formation?” Hepatology, vol. 55, no. 5, pp. 1313–1316, 2012. View at Publisher · View at Google Scholar
  7. R. H. Eckel, S. M. Grundy, and P. Z. Zimmet, “The metabolic syndrome,” The Lancet, vol. 365, no. 9468, pp. 1415–1428, 2005. View at Publisher · View at Google Scholar · View at Scopus
  8. S. M. Grundy, “Metabolic syndrome scientific statement by the American heart association and the national heart, lung, and blood institute,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 25, no. 11, pp. 2243–2244, 2005. View at Publisher · View at Google Scholar · View at Scopus
  9. S. M. Grundy and J. P. Barnett, “Metabolic and health complications of obesity,” Disease-a-Month, vol. 36, no. 12, pp. 641–731, 1990. View at Scopus
  10. S. M. Grundy, J. I. Cleeman, S. R. Daniels et al., “Diagnosis and management of the metabolic syndrome: an American heart association/national heart, lung, and blood institute scientific statement,” Circulation, vol. 112, no. 17, pp. 2735–2752, 2005. View at Publisher · View at Google Scholar · View at Scopus
  11. C. J. Tsai, M. F. Leitzmann, W. C. Willett, and E. L. Giovannucci, “Prospective study of abdominal adiposity and gallstone disease in US men,” The American Journal of Clinical Nutrition, vol. 80, no. 1, pp. 38–44, 2004. View at Scopus
  12. N. Méndez-Sánchez, N. C. Chavez-Tapia, D. Motola-Kuba et al., “Metabolic syndrome as a risk factor for gallstone disease,” World Journal of Gastroenterology, vol. 11, no. 11, pp. 1653–1657, 2005. View at Scopus
  13. F. Nervi, J. F. Miquel, M. Alvarez et al., “Gallbladder disease is associated with insulin resistance in a high risk Hispanic population,” Journal of Hepatology, vol. 45, no. 2, pp. 299–305, 2006. View at Publisher · View at Google Scholar · View at Scopus
  14. N. Ata, M. Kucukazman, B. Yavuz et al., “The metabolic syndrome is associated with complicated gallstone disease,” Canadian Journal of Gastroenterology, vol. 25, no. 5, pp. 274–276, 2011.
  15. D. Q. Wang, D. E. Cohen, and M. C. Carey, “Biliary lipids and cholesterol gallstone disease,” Journal of Lipid Research, vol. 50, supplement, pp. S406–S411, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. E. A. Mazzio and K. F. Soliman, “Basic concepts of epigenetics: impact of environmental signals on gene expression,” Epigenetics, vol. 7, no. 2, pp. 119–130, 2012. View at Publisher · View at Google Scholar
  17. P. Portincasa, A. Moschetta, and G. Palasciano, “Cholesterol gallstone disease,” The Lancet, vol. 368, no. 9531, pp. 230–239, 2006. View at Publisher · View at Google Scholar · View at Scopus
  18. A. F. Hofmann, A. Amelsberg, and E. Vansonnenberg, “Pathogenesis and treatment of gallstones,” The New England Journal of Medicine, vol. 328, 25, pp. 1854–1855, 1993.
  19. J. T. Lamont and M. C. Carey, “Cholesterol gallstone formation. 2. Pathobiology and pathomechanics,” Progress in liver diseases, vol. 10, pp. 165–191, 1992. View at Scopus
  20. P. Portincasa, A. Di Ciaula, G. Baldassarre et al., “Gallbladder motel function in gallstone patients: sonographic and in vitro studies on the role of gallstones; smooth muscle function and gallbladder wall inflammation,” Journal of Hepatology, vol. 21, no. 3, pp. 430–440, 1994. View at Publisher · View at Google Scholar · View at Scopus
  21. D. Q. Wang, B. A. Neuschwander-Tetri, and P. Portincasa, The Biliary System, Morgan & Claypool Life Sciences, Princeton, NJ, USA, 2012.
  22. F. Lammert and J. F. Miquel, “Gallstone disease: from genes to evidence-based therapy,” Journal of Hepatology, vol. 48, supplement 1, pp. S124–S135, 2008. View at Publisher · View at Google Scholar · View at Scopus
  23. F. Lammert and T. Sauerbruch, “Mechanisms of disease: the genetic epidemiology of gallbladder stones,” Nature Clinical Practice Gastroenterology and Hepatology, vol. 2, no. 9, pp. 423–433, 2005. View at Publisher · View at Google Scholar · View at Scopus
  24. P. Portincasa, A. Di Ciaula, H. H. Wang et al., “Coordinate regulation of gallbladder motor function in the gut-liver axis,” Hepatology, vol. 47, no. 6, pp. 2112–2126, 2008. View at Publisher · View at Google Scholar · View at Scopus
  25. P. Portincasa, A. Moschetta, F. Puglisi, and D. Q. H. Wang, “Medical treatment of gallstone disease,” in Biliary Lithiasis: Basic Science, Current Diagnosis and Management, G. Borzellino and C. Cordiano, Eds., pp. 149–157, Springer Italia S.r.l., Milan, Italy, 2008.
  26. D. Q. H. Wang, L. Zhang, and H. H. Wang, “High cholesterol absorption efficiency and rapid biliary secretion of chylomicron remnant cholesterol enhance cholelithogenesis in gallstone-susceptible mice,” Biochimica et Biophysica Acta, vol. 1733, no. 1, pp. 90–99, 2005. View at Publisher · View at Google Scholar · View at Scopus
  27. H. H. Wang, P. Portincasa, and D. Q. H. Wang, “Molecular pathophysiology and physical chemistry of cholesterol gallstones,” Frontiers in Bioscience, vol. 13, no. 2, pp. 401–423, 2008. View at Publisher · View at Google Scholar · View at Scopus
  28. H. Wittenburg and F. Lammert, “Genetic predisposition to gallbladder stones,” Seminars in Liver Disease, vol. 27, no. 1, pp. 109–121, 2007. View at Publisher · View at Google Scholar · View at Scopus
  29. D. Q. H. Wang and N. H. Afdhal, “Gallstone disease,” in Sleisenger and Fordtran's Gastrointestinal and Liver Disease, M. Feldman, L. S. Friedman, and L. J. Brand, Eds., vol. 9, pp. 1089–1120, Elsevier, Philadelphia, Pa, USA, 2010.
  30. P. Portincasa and G. Calamita, “Water channel proteins in bile formation and flow in health and disease: when immiscible becomes miscible,” Molecular Aspects of Medicine, vol. 33, no. 5-6, pp. 651–664, 2012. View at Publisher · View at Google Scholar
  31. W. H. Admirand and D. M. Small, “The physicochemical basis of cholesterol gallstone formation in man,” Journal of Clinical Investigation, vol. 47, no. 5, pp. 1043–1052, 1968. View at Scopus
  32. D. Q. H. Wang and M. C. Carey, “Characterization of crystallization pathways during cholesterol precipitation from human gallbladder biles: identical pathways to corresponding model biles with three predominating sequences,” Journal of Lipid Research, vol. 37, no. 12, pp. 2539–2549, 1996. View at Scopus
  33. J. J. Clarenbach, M. Reber, D. Lütjohann, K. von Bergmann, and T. Sudhop, “The lipid-lowering effect of ezetimibe in pure vegetarians,” Journal of Lipid Research, vol. 47, no. 12, pp. 2820–2824, 2006. View at Publisher · View at Google Scholar · View at Scopus
  34. K. F. Kozarsky, M. H. Donahee, A. Rigotti, S. N. Iqbal, E. R. Edelman, and M. Krieger, “Overexpression of the HDL receptor SR-BI alters plasma HDL and bile cholesterol levels,” Nature, vol. 387, no. 6631, pp. 414–417, 1997. View at Publisher · View at Google Scholar · View at Scopus
  35. S. J. Robins and J. M. Fasulo, “High density lipoproteins, but not other lipoproteins, provide a vehicle for sterol transport to bile,” Journal of Clinical Investigation, vol. 99, no. 3, pp. 380–384, 1997. View at Scopus
  36. E. Sehayek, J. G. Ono, S. Shefer et al., “Biliary cholesterol excretion: a novel mechanism that regulates dietary cholesterol absorption,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 17, pp. 10194–10199, 1998. View at Publisher · View at Google Scholar · View at Scopus
  37. J. F. Oram and J. W. Heinecke, “ATP-binding cassette transporter A1: a cell cholesterol exporter that protects against cardiovascular disease,” Physiological Reviews, vol. 85, no. 4, pp. 1343–1372, 2005. View at Publisher · View at Google Scholar · View at Scopus
  38. Y. A. Kesaniemi and T. A. Miettinen, “Cholesterol absorption efficiency regulates plasma cholesterol level in the Finnish population,” European Journal of Clinical Investigation, vol. 17, no. 5, pp. 391–395, 1987. View at Scopus
  39. M. S. Bosner, L. G. Lange, W. F. Stenson, and R. E. Ostlund Jr., “Percent cholesterol absorption in normal women and men quantified with dual stable isotopic tracers and negative ion mass spectrometry,” Journal of Lipid Research, vol. 40, no. 2, pp. 302–308, 1999. View at Scopus
  40. S. W. Altmann, H. R. Davis Jr., L. J. Zhu et al., “Niemann-pick C1 like 1 protein is critical for intestinal cholesterol absorption,” Science, vol. 303, no. 5661, pp. 1201–1204, 2004. View at Publisher · View at Google Scholar · View at Scopus
  41. D. Q. H. Wang, “Regulation of intestinal cholesterol absorption,” Annual Review of Physiology, vol. 69, pp. 221–248, 2007. View at Publisher · View at Google Scholar · View at Scopus
  42. D. Q. H. Wang and S. P. Lee, “Physical chemistry of intestinal absorption of biliary cholesterol in mice,” Hepatology, vol. 48, no. 1, pp. 177–185, 2008. View at Publisher · View at Google Scholar · View at Scopus
  43. S. D. Turley and J. M. Dietschy, “The metabolism and excretion of cholesterol by the liver,” in The Liver: Biology and Pathobiology, I. M. Arias, W. B. Iakoby, H. Popper, D. Schachter, and D. A. Shafritz, Eds., pp. 617–641, Raven Press, New York, NY, USA, 1988.
  44. M. A. Long, E. W. Kaler, and S. P. Lee, “Structural characterization of the micelle-vesicle transition in lecithin-bile salt solutions,” Biophysical Journal, vol. 67, no. 4, pp. 1733–1742, 1994. View at Scopus
  45. S. H. Quarfordt, B. Oswald, B. Landis, H. S. Xu, S. H. Zhang, and N. Maeda, “In vivo cholesterol kinetics in apolipoprotein E-deficient and control mice,” Journal of Lipid Research, vol. 36, no. 6, pp. 1227–1235, 1995. View at Scopus
  46. S. J. Robins and H. Brunengraber, “Origin of biliary cholesterol and lecithin in the rat: contribution of new synthesis and preformed hepatic stores,” Journal of Lipid Research, vol. 23, no. 4, pp. 604–608, 1982. View at Scopus
  47. C. C. Schwartz, M. Berman, and Z. R. Vlahcevic, “Multicompartmental analysis of cholesterol metabolism in man. Characterization of the hepatic bile acid and biliary cholesterol precursor sites,” Journal of Clinical Investigation, vol. 61, no. 2, pp. 408–423, 1978. View at Scopus
  48. Q. Chen, W. J. Li, Y. Y. Wan, C. D. Yu, and W. G. Li, “Fibroblast growth factor receptor 4 Gly388Arg polymorphism associated with severity of gallstone disease in a Chinese population,” Genetics and Molecular Research, vol. 11, no. 1, pp. 548–555, 2012. View at Publisher · View at Google Scholar
  49. S. W. Beaven and P. Tontonoz, “Nuclear receptors in lipid metabolism: targeting the heart of dyslipidemia,” Annual Review of Medicine, vol. 57, pp. 313–329, 2006. View at Publisher · View at Google Scholar · View at Scopus
  50. D. J. Peet, B. A. Janowski, and D. J. Mangelsdorf, “The LXRs: a new class of oxysterol receptors,” Current Opinion in Genetics and Development, vol. 8, no. 5, pp. 571–575, 1998. View at Publisher · View at Google Scholar · View at Scopus
  51. P. Tontonoz and D. J. Mangelsdorf, “Liver X receptor signaling pathways in cardiovascular disease,” Molecular Endocrinology, vol. 17, no. 6, pp. 985–993, 2003. View at Publisher · View at Google Scholar · View at Scopus
  52. H. Uppal, Y. Zhai, A. Gangopadhyay et al., “Activation of liver X receptor sensitizes mice to gallbladder cholesterol crystallization,” Hepatology, vol. 47, no. 4, pp. 1331–1342, 2008. View at Publisher · View at Google Scholar · View at Scopus
  53. C. J. Tsai, M. F. Leitzmann, W. C. Willett, and E. L. Giovannucci, “Statin use and the risk of cholecystectomy in women,” Gastroenterology, vol. 136, no. 5, pp. 1593–1600, 2009. View at Publisher · View at Google Scholar · View at Scopus
  54. R. Erichsen, T. Frøslev, T. L. Lash, L. Pedersen, and H. T. Sørensen, “Long-term statin use and the risk of gallstone disease: a population-based case-control study,” The American Journal of Epidemiology, vol. 173, no. 2, pp. 162–170, 2011. View at Publisher · View at Google Scholar · View at Scopus
  55. B. A. Chapman, M. J. Burt, R. J. Chisholm, R. B. Allan, K. H. J. Yeo, and A. G. Ross, “Dissolution of gallstones with simvastatin, an HMG CoA reductase inhibitor,” Digestive Diseases and Sciences, vol. 43, no. 2, pp. 349–353, 1998. View at Publisher · View at Google Scholar · View at Scopus
  56. D. S. Hanson and W. C. Duane, “Effects of lovastatin and chenodiol on bile acid synthesis, bile lipid composition, and biliary lipid secretion in healthy human subjects,” Journal of Lipid Research, vol. 35, no. 8, pp. 1462–1468, 1994. View at Scopus
  57. J. W. A. Smit, K. J. van Erpecum, P. Portincasa, W. Renooij, D. W. Erkelens, and G. P. van Berge-Henegouwen, “Effects of simvastatin and cholestyramine on bile lipid composition and gall bladder motility in patients with hypercholesterolaemia,” Gut, vol. 37, no. 5, pp. 654–659, 1995. View at Scopus
  58. J. C. Mitchell, G. M. Logan, B. G. Stone, and W. C. Duane, “Effects of lovastatin on biliary lipid secretion and bile acid metabolism in humans,” Journal of Lipid Research, vol. 32, no. 1, pp. 71–78, 1991. View at Scopus
  59. J. L. Smith, P. D. Roach, L. N. Wittenberg et al., “Effects of simvastatin on hepatic cholesterol metabolism, bile lithogenicity and bile acid hydrophobicity in patients with gallstones,” Journal of Gastroenterology and Hepatology, vol. 15, no. 8, pp. 871–879, 2000. View at Publisher · View at Google Scholar · View at Scopus
  60. H. Vanhanen, Y. A. Kesaniemi, and T. A. Miettinen, “Pravastatin lowers serum cholesterol, cholesterol-precursor sterols, fecal steroids, and cholesterol absorption in man,” Metabolism: Clinical and Experimental, vol. 41, no. 6, pp. 588–595, 1992. View at Publisher · View at Google Scholar · View at Scopus
  61. F. Lammert, D. Q. H. Wang, B. Paigen, and M. C. Carey, “Phenotypic characterization of Lith genes that determine susceptibility to cholesterol cholelithiasis in inbred mice: integrated activities of hepatic lipid regulatory enzymes,” Journal of Lipid Research, vol. 40, no. 11, pp. 2080–2090, 1999. View at Scopus
  62. S. M. Grundy, A. L. Metzger, and R. D. Adler, “Mechanisms of lithogenic bile formation in American Indian women with cholesterol gallstones,” Journal of Clinical Investigation, vol. 51, no. 12, pp. 3026–3043, 1972. View at Scopus
  63. P. H. Key, G. G. Bonorris, and J. W. Marks, “Biliary lipid synthesis and secretion in gallstone patients before and during treatment with chenodeoxycholic acid,” Journal of Laboratory and Clinical Medicine, vol. 95, no. 6, pp. 816–826, 1980. View at Scopus
  64. F. O. Nervi, C. F. Covarrubias, V. D. Valdivieso, B. O. Ronco, A. Solari, and J. Tocornal, “Hepatic cholesterogenesis in Chileans with cholesterol gallstone disease. Evidence for sex differences in the regulation of hepatic cholesterol metabolism,” Gastroenterology, vol. 80, no. 3, pp. 539–545, 1981. View at Scopus
  65. G. Salen, G. Nicolau, S. Shefer, and E. H. Mosbach, “Hepatic cholesterol metabolism in patients with gallstones,” Gastroenterology, vol. 69, no. 3, pp. 676–684, 1975. View at Scopus
  66. E. F. Stange and J. M. Dietschy, “Cholesterol absorption and metabolism by the intestinal epithelium,” in Sterols and Bile Acids, H. Danielsson and J. Sjovall, Eds., pp. 121–149, Elsevier, Amsterdam, The Netherlands, 1985.
  67. H. Y. I. Mok, K. von Bergmann, and S. M. Grundy, “Effects of continuous and intermittent feeding on biliary lipid outputs in man: application for measurements of intestinal absorption of cholesterol and bile acids,” Journal of Lipid Research, vol. 20, no. 3, pp. 389–398, 1979. View at Scopus
  68. K. K. Buhman, M. Accad, S. Novak et al., “Resistance to diet-induced hypercholesterolemia and gallstone formation in ACAT2-deficient mice,” Nature Medicine, vol. 6, no. 12, pp. 1341–1347, 2000. View at Publisher · View at Google Scholar · View at Scopus
  69. H. H. Wang and D. Q. H. Wang, “Reduced susceptibility to cholesterol gallstone formation in mice that do not produce apolipoprotein B48 in the intestine,” Hepatology, vol. 42, no. 4, pp. 894–904, 2005. View at Publisher · View at Google Scholar · View at Scopus
  70. L. Amigo, V. Quiones, P. Mardones et al., “Impaired biliary cholesterol secretion and decreased gallstone formation in apolipoprotein E-deficient mice fed a high-cholesterol diet,” Gastroenterology, vol. 118, no. 4, pp. 772–779, 2000. View at Scopus
  71. L. DenBesten, W. E. Connor, and S. Bell, “The effect of dietary cholesterol on the composition of human bile,” Surgery, vol. 73, no. 2, pp. 266–273, 1973. View at Scopus
  72. H. Dam, I. Prange, M. K. Jensen, H. E. Kallehauge, and H. J. Fenger, “Studies on human bile—IV. Influence of ingestion of cholesterol in the form of eggs on the composition of bile in healthy subjects,” Zeitschrift für Ernährungswissenschaft, vol. 10, no. 3, pp. 178–187, 1971. View at Publisher · View at Google Scholar · View at Scopus
  73. E. Andersen and K. Hellstrom, “The effect of cholesterol feeding on bile acid kinetics and biliary lipids in normolipidemic and hypertriglyceridemic subjects,” Journal of Lipid Research, vol. 20, no. 8, pp. 1020–1027, 1979. View at Scopus
  74. D. W. T. Lee, C. J. Gilmore, G. Bonorris et al., “Effect of dietary cholesterol on biliary lipids in patients with gallstones and normal subjects,” The American Journal of Clinical Nutrition, vol. 42, no. 3, pp. 414–420, 1985. View at Scopus
  75. T. Gilat, C. Feldman, and Z. Halpern, “An increased familial frequency of gallstones,” Gastroenterology, vol. 84, no. 2, pp. 242–246, 1983. View at Scopus
  76. R. E. Sampliner, P. H. Bennett, L. J. Comess, F. A. Rose, and T. A. Burch, “Gallbladder disease in pima indians. Demonstration of high prevalence and early onset by cholecystography,” The New England Journal of Medicine, vol. 283, no. 25, pp. 1358–1364, 1970. View at Scopus
  77. S. K. Sarin, V. S. Negi, R. Dewan, S. Sasan, and A. Saraya, “High familial prevalence of gallstones in the first-degree relatives of gallstone patients,” Hepatology, vol. 22, no. 1, pp. 138–141, 1995. View at Scopus
  78. C. S. Stokes, M. Krawczyk, and F. Lammert, “Gallstones: environment, lifestyle and genes,” Digestive Diseases, vol. 29, no. 2, pp. 191–201, 2011. View at Publisher · View at Google Scholar · View at Scopus
  79. H. Wittenburg, “Hereditary liver disease: gallstones,” Best Practice and Research: Clinical Gastroenterology, vol. 24, no. 5, pp. 747–756, 2010. View at Publisher · View at Google Scholar · View at Scopus
  80. D. Katsika, A. Grjibovski, C. Einarsson, F. Lammert, P. Lichtenstein, and H. U. Marschall, “Genetic and environmental influences on symptomatic gallstone disease: a Swedish study of 43,141 twin pairs,” Hepatology, vol. 41, no. 5, pp. 1138–1143, 2005. View at Publisher · View at Google Scholar · View at Scopus
  81. D. Katsika, P. Magnusson, M. Krawczyk et al., “Gallstone disease in Swedish twins: risk is associated with ABCG8 D19H genotype,” Journal of Internal Medicine, vol. 268, no. 3, pp. 279–285, 2010. View at Publisher · View at Google Scholar · View at Scopus
  82. M. Acalovschi, A. Ciocan, O. Mostean et al., “Are plasma lipid levels related to ABCG5/ABCG8 polymorphisms? A preliminary study in siblings with gallstones,” European Journal of Internal Medicine, vol. 17, no. 7, pp. 490–494, 2006. View at Publisher · View at Google Scholar · View at Scopus
  83. H. Gylling, M. Hallikainen, J. Pihlajamäki et al., “Polymorphisms in the ABCG5 and ABCG8 genes associate with cholesterol absorption and insulin sensitivity,” Journal of Lipid Research, vol. 45, no. 9, pp. 1660–1665, 2004. View at Publisher · View at Google Scholar · View at Scopus
  84. S. C. Chuang, E. Hsi, and K. T. Lee, “Mucin genes in gallstone disease,” Clinica Chimica Acta, vol. 413, no. 19-20, pp. 1466–1471, 2012. View at Publisher · View at Google Scholar
  85. S. C. Chuang, E. Hsi, S. N. Wang, M. L. Yu, K. T. Lee, and S. H. Juo, “Polymorphism at the mucin-like protocadherin gene influences susceptibility to gallstone disease,” Clinica Chimica Acta, vol. 412, no. 23-24, pp. 2089–2093, 2011. View at Publisher · View at Google Scholar
  86. H. L. Xu, J. R. Cheng, G. Andreotti et al., “Cholesterol metabolism gene polymorphisms and the risk of biliary tract cancers and stones: a population-based case-control study in Shanghai, China,” Carcinogenesis, vol. 32, no. 1, pp. 58–62, 2011. View at Scopus
  87. L. M. Berends and S. E. Ozanne, “Early determinants of type-2 diabetes,” Best Practice and Research Clinical Endocrinology and Metabolism, vol. 26, no. 5, pp. 569–580, 2012. View at Publisher · View at Google Scholar
  88. E. R. Gilbert and D. Liu, “Epigenetics: the missing link to understanding beta-cell dysfunction in the pathogenesis of type 2 diabetes,” Epigenetics, vol. 7, no. 8, pp. 841–852, 2012. View at Publisher · View at Google Scholar
  89. M. S. Martin-Gronert and S. E. Ozanne, “Metabolic programming of insulin action and secretion,” Diabetes, Obesity and Metabolism, vol. 14, supplement 3, pp. 29–39, 2012. View at Publisher · View at Google Scholar
  90. F. I. Milagro, M. L. Mansego, M. C. De, and J. A. Martinez, “Dietary factors, epigenetic modifications and obesity outcomes: progresses and perspectives,” Molecular Aspects of Medicine, 2012. View at Publisher · View at Google Scholar
  91. S. Sookoian and C. J. Pirola, “DNA methylation and hepatic insulin resistance and steatosis,” Current Opinion in Clinical Nutrition and Metabolic Care, vol. 15, no. 4, pp. 350–356, 2012. View at Publisher · View at Google Scholar
  92. J. Wang, Z. Wu, D. Li et al., “Nutrition, epigenetics, and metabolic syndrome,” Antioxidants and Redox Signaling, vol. 17, no. 2, pp. 282–301, 2012. View at Publisher · View at Google Scholar
  93. M. A. Dawson and T. Kouzarides, “Cancer epigenetics: from mechanism to therapy,” Cell, vol. 150, no. 1, pp. 12–27, 2012. View at Publisher · View at Google Scholar
  94. M. A. Dawson, T. Kouzarides, and B. J. Huntly, “Targeting epigenetic readers in cancer,” The New England Journal of Medicine, vol. 367, no. 7, pp. 647–657, 2012. View at Publisher · View at Google Scholar
  95. C. Marsit and B. Christensen, “Blood-derived DNA methylation markers of cancer risk,” Advances in Experimental Medicine and Biology, vol. 754, pp. 233–252, 2013. View at Publisher · View at Google Scholar
  96. S. Udali, P. Guarini, S. Moruzzi, S. W. Choi, and S. Friso, “Cardiovascular epigenetics: from DNA methylation to microRNAs,” Molecular Aspects of Medicine, 2012. View at Publisher · View at Google Scholar
  97. J. B. Kwok, “Role of epigenetics in Alzheimers and Parkinsons disease,” Epigenomics, vol. 2, no. 5, pp. 671–682, 2010. View at Publisher · View at Google Scholar · View at Scopus
  98. J. A. Piedrahita, “The role of imprinted genes in fetal growth abnormalities,” Birth Defects Research A, vol. 91, no. 8, pp. 682–692, 2011. View at Publisher · View at Google Scholar · View at Scopus
  99. Y. J. Loke, B. Novakovic, M. Ollikainen et al., “The peri/postnatal epigenetic twins study (PETS),” Twin Research and Human Genetics, vol. 16, no. 1, pp. 13–20, 2013. View at Publisher · View at Google Scholar
  100. F. M. Low, P. D. Gluckman, and M. A. Hanson, “Developmental plasticity and epigenetic mechanisms underpinning metabolic and cardiovascular diseases,” Epigenomics, vol. 3, no. 3, pp. 279–294, 2011. View at Publisher · View at Google Scholar · View at Scopus
  101. R. Cong, Y. Jia, R. Li et al., “Maternal low-protein diet causes epigenetic deregulation of HMGCR and CYP7alpha1 in the liver of weaning piglets,” The Journal of Nutritional Biochemistry, vol. 23, no. 12, pp. 1647–1654, 2012. View at Publisher · View at Google Scholar
  102. G. Sohi, K. Marchand, A. Revesz, E. Arany, and D. B. Hardy, “Maternal protein restriction elevates cholesterol in adult rat offspring due to repressive changes in histone modifications at the cholesterol 7α-hydroxylase promoter,” Molecular Endocrinology, vol. 25, no. 5, pp. 785–798, 2011. View at Publisher · View at Google Scholar · View at Scopus
  103. T. F. Cheng, S. Choudhuri, and K. Muldoon-Jacobs, “Epigenetic targets of some toxicologically relevant metals: a review of the literature,” Journal of Applied Toxicology, vol. 32, no. 9, pp. 643–653, 2012. View at Publisher · View at Google Scholar
  104. R. Martinez-Zamudio and H. C. Ha, “Environmental epigenetics in metal exposure,” Epigenetics, vol. 6, no. 7, pp. 820–827, 2011. View at Publisher · View at Google Scholar · View at Scopus
  105. J. F. Reichard and A. Puga, “Effects of arsenic exposure on DNA methylation and epigenetic gene regulation,” Epigenomics, vol. 2, no. 1, pp. 87–104, 2010. View at Publisher · View at Google Scholar · View at Scopus
  106. N. Sadli, M. L. Ackland, M. D. De, A. J. Sinclair, and C. Suphioglu, “Effects of zinc and DHA on the epigenetic regulation of human neuronal cells,” Cellular Physiology and Biochemistry, vol. 29, no. 1-2, pp. 87–98, 2012. View at Publisher · View at Google Scholar
  107. B. Wang, Y. Li, C. Shao, Y. Tan, and L. Cai, “Cadmium and its epigenetic effects,” Current Medicinal Chemistry, vol. 19, no. 16, pp. 2611–2620, 2012. View at Publisher · View at Google Scholar
  108. T. Ding, M. McConaha, K. L. Boyd, K. G. Osteen, and K. L. Bruner-Tran, “Developmental dioxin exposure of either parent is associated with an increased risk of preterm birth in adult mice,” Reproductive Toxicology, vol. 31, no. 3, pp. 351–358, 2011. View at Publisher · View at Google Scholar · View at Scopus
  109. R. McKinlay, J. A. Plant, J. N. B. Bell, and N. Voulvoulis, “Calculating human exposure to endocrine disrupting pesticides via agricultural and non-agricultural exposure routes,” Science of the Total Environment, vol. 398, no. 1–3, pp. 1–12, 2008. View at Publisher · View at Google Scholar · View at Scopus
  110. E. Nilsson, G. Larsen, M. Manikkam, C. Guerrero-Bosagna, M. I. Savenkova, and M. K. Skinner, “Environmentally induced epigenetic transgenerational inheritance of ovarian disease,” PloS ONE, vol. 7, no. 5, Article ID e36129, 2012. View at Publisher · View at Google Scholar
  111. T. Takeda, M. Fujii, J. Taura, Y. Ishii, and H. Yamada, “Dioxin silences gonadotropin expression in perinatal pups by inducing histone deacetylases: a new insight into the mechanism for the imprinting of sexual immaturity by dioxin,” The Journal of Biological Chemistry, vol. 287, pp. 18440–18450, 2012. View at Publisher · View at Google Scholar
  112. B. Weinhold, “More chemicals show epigenetic effects across generations,” Environmental Health Perspectives, vol. 120, article A228, 2012.
  113. A. Ferrari, E. Fiorino, M. Giudici et al., “Linking epigenetics to lipid metabolism: focus on histone deacetylases,” Molecular Membrane Biology, vol. 29, no. 7, pp. 257–266, 2012. View at Publisher · View at Google Scholar
  114. J. C. Chuang and P. A. Jones, “Epigenetics and microRNAs,” Pediatric Research, vol. 61, no. 5, pp. 24R–29R, 2007. View at Publisher · View at Google Scholar · View at Scopus
  115. W. Y. Tang and S. M. Ho, “Epigenetic reprogramming and imprinting in origins of disease,” Reviews in Endocrine and Metabolic Disorders, vol. 8, no. 2, pp. 173–182, 2007. View at Publisher · View at Google Scholar · View at Scopus
  116. J. A. Martinez, P. Cordero, J. Campion, and F. I. Milagro, “Interplay of early-life nutritional programming on obesity, inflammation and epigenetic outcomes,” The Proceedings of the Nutrition Society, vol. 71, no. 2, pp. 276–283, 2012. View at Publisher · View at Google Scholar
  117. S. Y. Rhee, Y. C. Hwang, J. T. Woo et al., “Blood lead is significantly associated with metabolic syndrome in Korean adults: an analysis based on the Korea national health and nutrition examination survey (KNHANES), 2008,” Cardiovascular Diabetology, vol. 12, no. 1, article 9, 2013. View at Publisher · View at Google Scholar
  118. S. Unisa, P. Jagannath, V. Dhir, C. Khandelwal, L. Sarangi, and T. K. Roy, “Population-based study to estimate prevalence and determine risk factors of gallbladder diseases in the rural Gangetic basin of North India,” HPB, vol. 13, no. 2, pp. 117–125, 2011. View at Publisher · View at Google Scholar · View at Scopus
  119. V. Ambros, “The functions of animal microRNAs,” Nature, vol. 431, no. 7006, pp. 350–355, 2004. View at Publisher · View at Google Scholar · View at Scopus
  120. D. P. Bartel, “MicroRNAs: genomics, biogenesis, mechanism, and function,” Cell, vol. 116, no. 2, pp. 281–297, 2004. View at Publisher · View at Google Scholar · View at Scopus
  121. D. P. Bartel, “MicroRNAs: target recognition and regulatory functions,” Cell, vol. 136, no. 2, pp. 215–233, 2009. View at Publisher · View at Google Scholar · View at Scopus
  122. K. J. Moore, K. J. Rayner, Y. Suárez, and C. Fernández-Hernando, “MicroRNAs and cholesterol metabolism,” Trends in Endocrinology and Metabolism, vol. 21, no. 12, pp. 699–706, 2010. View at Publisher · View at Google Scholar · View at Scopus
  123. M. G. Ross and M. H. Beall, “Adult sequelae of intrauterine growth restriction,” Seminars in Perinatology, vol. 32, no. 3, pp. 213–218, 2008. View at Publisher · View at Google Scholar · View at Scopus
  124. B. Lamarche, S. Lemieux, G. R. Dagenais, and J. P. Després, “Visceral obesity and the risk of ischaemic heart disease: insights from the Québec cardiovascular study,” Growth Hormone and IGF Research, vol. 8, pp. 1–8, 1998. View at Scopus
  125. M. Makishima, A. Y. Okamoto, J. J. Repa et al., “Identification of a nuclear receptor for bite acids,” Science, vol. 284, no. 5418, pp. 1362–1365, 1999. View at Publisher · View at Google Scholar · View at Scopus
  126. D. J. Parks, S. G. Blanchard, R. K. Bledsoe et al., “Bile acids: natural ligands for an orphan nuclear receptor,” Science, vol. 284, no. 5418, pp. 1365–1368, 1999. View at Publisher · View at Google Scholar · View at Scopus
  127. J. J. Repa and D. J. Mangelsdorf, “The liver X receptor gene team: potential new players in atherosclerosis,” Nature Medicine, vol. 8, no. 11, pp. 1243–1248, 2002. View at Publisher · View at Google Scholar · View at Scopus
  128. N. Y. Kalaany and D. J. Mangelsdorf, “LXRs and FXR: the Yin and Yang of cholesterol and fat metabolism,” Annual Review of Physiology, vol. 68, pp. 159–191, 2006. View at Publisher · View at Google Scholar · View at Scopus
  129. J. Lee, S. Seok, P. Yu et al., “Genomic analysis of hepatic farnesoid X receptor binding sites reveals altered binding in obesity and direct gene repression by farnesoid X receptor in mice,” Hepatology, vol. 56, no. 1, pp. 108–117, 2012. View at Publisher · View at Google Scholar
  130. O. de Bari, B. A. Neuschwander-Tetri, M. Liu, P. Portincasa, and D. Q. Wang, “Ezetimibe: its novel effects on the prevention and the treatment of cholesterol gallstones and nonalcoholic fatty liver disease,” Journal of Lipids, vol. 2012, Article ID 302847, 16 pages, 2012. View at Publisher · View at Google Scholar