Skip to main content

Advertisement

Log in

Association of SIRT1 gene polymorphism and its expression for the risk of alcoholic fatty liver disease in the Han population

  • Original Article
  • Published:
Hepatology International Aims and scope Submit manuscript

Abstract

Objective

To investigate the associations between SIRT1 polymorphisms and their expression in patients with alcoholic fatty liver disease (AFLD).

Methods

A total of 268 heavy drinkers were divided into the AFLD group (n = 176) and alcoholic control (n = 92) and 237 light-/non-drinkers into the NAFLD (non-AFLD) group (n = 117) and healthy control (n = 120). The genotyping of SIRT1 (rs33957861, rs11599176, rs12413112 and rs35689145) was detected by the Sequenom MassARRAY iPLEX test. The mRNA and protein expressions of SIRT1 were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assays (ELISA), respectively.

Results

SIRT1 gene rs33957861 and rs11599176 polymorphisms significantly reduce the risk of NAFLD and AFLD, while rs35689145 remarkably increases the risk. Haplotypes of AAAA (rs33957861–rs11599176–rs12413112–rs35689145), AAAA, CAGA and CGAA can appreciably lower the presence of AFLD, but CAAG had an elevated AFLD risk. Besides, in the NAFLD and AFLD groups, a decreased BMI was found in the mutant genotype carriers of rs33957861, rs11599176 and rs12413112, but an increased BMI was observed in the rs35689145 mutant genotype carriers when compared to those with the wild-type homozygous genotype ones. Furthermore, rs33957861 C>T, rs11599176 A>G and BMI were independent risk factors of AFLD. There was no difference among four SNPs of SIRT1 and its mRNA and protein expressions in all groups.

Conclusion

SIRT1 polymorphisms and their expression were associated with the presence of AFLD, and there was a close relationship among four SNPs and BMI in AFLD patients, but no SNP was related to its expression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Yu X, Xu Y, Zhang S, Sun J, Liu P, Xiao L, et al. Quercetin attenuates chronic ethanol-induced hepatic mitochondrial damage through enhanced mitophagy. Nutrients 2016;8(1):27

    Article  PubMed Central  Google Scholar 

  2. Fan JG. Epidemiology of alcoholic and nonalcoholic fatty liver disease in China. J Gastroenterol Hepatol 2013;28(Suppl 1):11–17

    Article  PubMed  Google Scholar 

  3. Rogers CQ, Ajmo JM, You M. Adiponectin and alcoholic fatty liver disease. IUBMB Life 2008;60:790–797

    Article  CAS  PubMed  Google Scholar 

  4. You M, Rogers CQ. Adiponectin: a key adipokine in alcoholic fatty liver. Exp Biol Med 2009;234:850–859

    Article  CAS  Google Scholar 

  5. Anstee QM, Daly AK, Day CP. Genetics of alcoholic and nonalcoholic fatty liver disease. Semin Liver Dis 2011;31:128–146

    Article  CAS  PubMed  Google Scholar 

  6. Salameh H, Raff E, Erwin A, Seth D, Nischalke HD, Falleti E, et al. PNPLA3 gene polymorphism is associated with predisposition to and severity of alcoholic liver disease. Am J Gastroenterol 2015;110:846–856

    Article  CAS  PubMed  Google Scholar 

  7. Yin H, Hu M, Liang X, Ajmo JM, Li X, Bataller R, et al. Deletion of SIRT1 from hepatocytes in mice disrupts lipin-1 signaling and aggravates alcoholic fatty liver. Gastroenterology 2014;146:801–811

    Article  CAS  PubMed  Google Scholar 

  8. Zhang Y, Geng C, Liu X, Li M, Gao M, Liu X, et al. Celastrol ameliorates liver metabolic damage caused by a high-fat diet through Sirt1. Mol Metab 2017;6:138–147

    Article  CAS  PubMed  Google Scholar 

  9. Chen YR, Lai YL, Lin SD, Li XT, Fu YC, Xu WC. SIRT1 interacts with metabolic transcriptional factors in the pancreas of insulin-resistant and calorie-restricted rats. Mol Biol Rep 2013;40:3373–3380

    Article  CAS  PubMed  Google Scholar 

  10. Dong Y, Guo T, Traurig M, Mason CC, Kobes S, Perez J, et al. SIRT1 is associated with a decrease in acute insulin secretion and a sex specific increase in risk for type 2 diabetes in Pima Indians. Mol Genet Metab 2011;104:661–665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kilic U, Gok O, Elibol-Can B, Ozgen IT, Erenberk U, Uysal O, et al. SIRT1 gene variants are related to risk of childhood obesity. Eur J Pediatr 2015;174:473–479

    Article  CAS  PubMed  Google Scholar 

  12. Bai T, Yang Y, Yao YL, Sun P, Lian LH, Wu YL, et al. Betulin alleviated ethanol-induced alcoholic liver injury via SIRT1/AMPK signaling pathway. Pharmacol Res 2016;105:1–12

    Article  CAS  PubMed  Google Scholar 

  13. Inaoka Y, Osawa M, Mukasa N, Miyashita K, Satoh F, Kakimoto Y. Allelic imbalance of mRNA associated with alpha2-HS glycoprotein (Fetuin-A) polymorphism. Dis Markers 2015;2015:865053

    Article  PubMed  PubMed Central  Google Scholar 

  14. Hu Y, Wang L, Chen S, Liu X, Li H, Lu X, et al. Association between the SIRT1 mRNA expression and acute coronary syndrome. J Atheroscler Thromb 2015;22:165–182

    Article  CAS  PubMed  Google Scholar 

  15. Razi S, Cogger VC, Kennerson M, Benson VL, McMahon AC, Blyth FM, et al. SIRT1 polymorphisms and serum-induced SIRT1 protein expression in aging and frailty: the CHAMP study. J Gerontol Ser A Biol Sci Med Sci 2017;72:870–876

    Article  Google Scholar 

  16. Muthuswamy V. The new 2013 seventh version of the Declaration of Helsinki—more old wine in a new bottle? Indian J Med Ethics 2014;11:2–4

    PubMed  Google Scholar 

  17. Rey JW, Noetel A, Hardt A, et al. Pro12Ala polymorphism of the peroxisome proliferator-activated receptor γ2 in patients with fatty liver diseases. World J Gastroenterol 2010;16:5830–5837

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Beuers U. European association for the study of the liver. BMJ 1969;3:711–712

    Article  Google Scholar 

  19. Muratori L, Muratori P, Lanzoni G, Ferri S, Lenzi M. Application of the 2010 American Association for the study of liver diseases criteria of remission to a cohort of Italian patients with autoimmune hepatitis. Hepatology 2010;52:1857 (author reply 1857–1858)

    Article  PubMed  Google Scholar 

  20. Polyzos SA, Kountouras J, Mantzoros CS. Adipose tissue, obesity and non-alcoholic fatty liver disease. Minerva Endocrinol 2017;42:92–108

    PubMed  Google Scholar 

  21. Lu X, Yuan ZY, Yan XJ, Lei F, Jiang JF, Yu X, et al. Effects of Angelica dahurica on obesity and fatty liver in mice. Chin J Nat Med 2016;14:641–652

    PubMed  Google Scholar 

  22. Yan H, Lu X, Gao Y, Luo J. Epidemiological investigation of fatty liver disease in Northwest China. Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chin J Hepatol 2015;23:622

    CAS  Google Scholar 

  23. Zheng J, Chen LL, Xiao F, Hu X, Deng X, Li H. Three single nucleotide variants of the SIRT1 gene are associated with overweight in a Chinese population: a case control study. Endocr J 2012;59:229–237

    Article  CAS  PubMed  Google Scholar 

  24. Zillikens MC, van Meurs JB, Rivadeneira F, Amin N, Hofman A, Oostra BA, et al. SIRT1 genetic variation is related to BMI and risk of obesity. Diabetes 2009;58:2828–2834

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Clark SJ, Falchi M, Olsson B, Jacobson P, Cauchi S, Balkau B, et al. Association of sirtuin 1 (SIRT1) gene SNPs and transcript expression levels with severe obesity. Obesity 2012;20:178–185

    Article  CAS  PubMed  Google Scholar 

  26. You M, Jogasuria A, Taylor C, Wu J. Sirtuin 1 signaling and alcoholic fatty liver disease. Hepatobiliary Surg Nutr 2015;4:88–100

    PubMed  PubMed Central  Google Scholar 

  27. Zhou J, Liu Y, Zhou D, Nie S, Zhao H, Jin G. Pathogenic role of the adiponectin-SIRT 1-AMPK signaling pathway in alcoholic fatty liver disease. Zhonghua Gan Zang Bing Za Zhi 2015;23:711–714

    CAS  PubMed  Google Scholar 

  28. You M, Liang X, Ajmo JM, Ness GC. Involvement of mammalian sirtuin 1 in the action of ethanol in the liver. Am J Physiol Gastrointest Liver Physiol 2008;294:G892–G898

    Article  CAS  PubMed  Google Scholar 

  29. Lieber CS, Leo MA, Wang X, Decarli LM. Effect of chronic alcohol consumption on Hepatic SIRT1 and PGC-1alpha in rats. Biochem Biophys Res Commun 2008;370:44–48

    Article  CAS  PubMed  Google Scholar 

  30. Bi L, Jiang Z, Zhou J. The role of lipin-1 in the pathogenesis of alcoholic fatty liver. Alcohol Alcohol 2015;50:146–151

    Article  PubMed  Google Scholar 

  31. Liang X, Hu M, Rogers CQ, Shen Z, You M. Role of SIRT1-FoxO1 signaling in dietary saturated fat-dependent upregulation of liver adiponectin receptor 2 in ethanol-administered mice. Antioxid Redox Signal 2011;15:425–435

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Shen Z, Ajmo JM, Rogers CQ, Liang X, Le L, Murr MM, et al. Role of SIRT1 in regulation of LPS- or two ethanol metabolites-induced TNF-alpha production in cultured macrophage cell lines. Am J Physiol Gastrointest Liver Physiol 2009;296:G1047–G1053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Caito S, Rajendrasozhan S, Cook S, Chung S, Yao H, Friedman AE, et al. SIRT1 is a redox-sensitive deacetylase that is post-translationally modified by oxidants and carbonyl stress. FASEB J Off Publ Fed Am Soc Exp Biol 2010;24:3145–3159

    CAS  Google Scholar 

Download references

Acknowledgements

We would like to express our thanks to the reviewers for their useful and suggestive comments on the current study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Wei Shen.

Ethics declarations

Funding

None.

Conflict of interest

Yeting Hou, Bingzhong Su, Ping Chen, Haijing Niu, Sheng Zhao, Ruijun Wang and Wei Shen have no conflict of interests to declare.

Ethical approval

The present study was approved by the Ethics Committee of The Affiliated Hospital of Inner Mongolia Medical University, in accordance with the Helsinki Declaration.

Informed consent

All included subjects were informed of the purpose of the study and provided signed informed consent.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hou, Y., Su, B., Chen, P. et al. Association of SIRT1 gene polymorphism and its expression for the risk of alcoholic fatty liver disease in the Han population. Hepatol Int 12, 56–66 (2018). https://doi.org/10.1007/s12072-017-9836-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12072-017-9836-8

Keywords

Navigation