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.
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Acknowledgements
We would like to express our thanks to the reviewers for their useful and suggestive comments on the current study.
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Yeting Hou, Bingzhong Su, Ping Chen, Haijing Niu, Sheng Zhao, Ruijun Wang and Wei Shen have no conflict of interests to declare.
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The present study was approved by the Ethics Committee of The Affiliated Hospital of Inner Mongolia Medical University, in accordance with the Helsinki Declaration.
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All included subjects were informed of the purpose of the study and provided signed informed consent.
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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
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DOI: https://doi.org/10.1007/s12072-017-9836-8