Association between the Polymorphism of the TM6SF2- rs58542926 Gene and Liver Damage and the Severity of Liver Fibrosis: A Meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

 SHIMing-qiao ¹ ,  CHENJie ² , WANGLan-lan ² , LIAOYun ² , ZHANGQi ² , YANLin ² , LIUXin-le ²

1. West China School of Medicine, Sichuan University, Chengdu 610041, China;
2. Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, China;

Corresponding author：

CHENJie, Email: chenjie_wch@163.com

Keywords：

TM6SF2; Liver fibrosis; Lipid metabolism; Non-alcoholic fatty liver disease; Meta-analysis

DOI：

10.7507/1672-2531.20160102

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objectives To systematically review the association between TM6SF2 (transmembrane six superfamily member 2- rs58592426) polymorphism and liver lesion and the severity of liver fibrosis. Methods We electronically searched databases including PubMed, CNKI, WanFang Data and CBM from inception to January 27, 2016, to collect cross-sectional studies about the association between the TM6SF2 polymorphism and the liver lesion and the severity of liver fibrosis. Two reviewers independently screened literature, extracted data and assessed the methodological quality included studies. Then, meta-analysis was performed using Stata 12.0 software. Results A total of 23 studies including 96 594 patients were included. The results of meta-analysis showed that: TM6SF2 polymorphism was associated with increased risk of the severity of liver fibrosis, the levels of TG, TC and LDL-C (all P values < 0.05). Carriers of the T allele showed lower levels of TG, TC, and LDL-C. Carriers of the T allele revealed higher levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) when compared with homozygous EE. Conclusion TM6SF2 polymorphism is associated with lipid traits in different population, the variants shows lower levels of lipid traits in blood serum and increases the risk of the severity of liver fibrosis and liver lesion.

Citation： SHIMing-qiao, CHENJie, WANGLan-lan, LIAOYun, ZHANGQi, YANLin, LIUXin-le. Association between the Polymorphism of the TM6SF2- rs58542926 Gene and Liver Damage and the Severity of Liver Fibrosis: A Meta-analysis. Chinese Journal of Evidence-Based Medicine, 2016, 16(6): 655-662. doi: 10.7507/1672-2531.20160102 Copy

1.	范慧宁, 陈尼维. 肝纤维化的流行病学研究进展. 国际消化病杂志, 2014, (1): 29-31.
2.	Ress C, Kaser S. Mechanisms of intrahepatic triglyceride accumulation. World Journal of Gastroenterology, 2016, 22(4): 1664-1673.
3.	Liu YL, Reeves HL, Burt AD, et al. TM6SF2 rs58542926 influences hepatic fibrosis progression in patients with non-alcoholic fatty liver disease. Nat Commun, 2014, 5: 4309.
4.	Coppola N, Rosa Z, Cirillo G, et al. TM6SF2 E167K variant is associated with severe steatosis in chronic hepatitis C, regardless of PNPLA3 polymorphism. Liver Int, 2015, 35(8): 1959-1963.
5.	Dongiovanni P, Petta S, Maglio C, et al. Transmembrane 6 superfamily member 2 gene variant disentangles nonalcoholic steatohepatitis from cardiovascular disease. Hepatology, 2015, 61(2): 506-514.
6.	Pietiainen V, Lindgren CM, Stefansson K, et al. TM6SF2 Glu167Lys polymorphism is associated with low levels of LDL-cholesterol and increased liver injury in obese children. Pediatr Obes, 2016, 11(2): 115-119.
7.	Petta S, Maida M, Grimaudo 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, 2016, 36(2): 198-204.
8.	Milano M, Aghemo A, Dongiovanni P, et al. Transmembrane 6 superfamily member 2 gene E167K variant impacts on steatosis and liver damage in chronic hepatitis C patients. Hepatology, 2015, 62(1): 111-117.
9.	Sookoian S, Castano GO, Scian R, et al. Genetic variation in transmembrane 6 superfamily member 2 and the risk of nonalcoholic fatty liver disease and histological disease severity. Hepatology, 2015, 61(2): 515-525.
10.	Goffredo M, Caprio S, Feldstein AE, et al. Role of the TM6SF2 rs58542926 in the pathogenesis of non-alcoholic pediatric fatty liver disease (NAFLD): A multiethnic study. Hepatology, 2016, 63(1): 117-125.
11.	Scorletti E, West AL, Bhatia L, et al. Treating liver fat and serum triglyceride levels in NAFLD, effects of PNPLA3 and TM6SF2 genotypes: Results from the WELCOME trial. J Hepatol, 2015, 63(6): 1476-1483.
12.	Mancina RM, Matikainen N, Maglio C, et al. Paradoxical dissociation between hepatic fat content and de novo lipogenesis due to PNPLA3 sequence variant. J Clin Endocrinol Metab, 2015, 100(5): E821-825.
13.	Kozlitina J, Smagris E, Stender S, et al. Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease. Nat Genet, 2014, 46(4): 352-356.
14.	Wong VW, Wong GL, Tse CH, et al. Prevalence of the TM6SF2 variant and non-alcoholic fatty liver disease in Chinese. Hepatology, 2014, 61(3): 708-709.
15.	Akuta N, Kawamura Y, Arase Y, et al. Relationships between Genetic Variations of PNPLA3, TM6SF2 and Histological Features of Nonalcoholic Fatty Liver Disease in Japan. Gut Liver, 2016, 10(3): 437-445.
16.	Arslanow A, Stokes CS, Weber SN, et al. The common PNPLA3 variant p.I148M is associated with liver fat contents as quantified by controlled attenuation parameter (CAP). Liver Int, 2016, 36(3): 418-426.

1. 范慧宁, 陈尼维. 肝纤维化的流行病学研究进展. 国际消化病杂志, 2014, (1): 29-31.
2. Ress C, Kaser S. Mechanisms of intrahepatic triglyceride accumulation. World Journal of Gastroenterology, 2016, 22(4): 1664-1673.
3. Liu YL, Reeves HL, Burt AD, et al. TM6SF2 rs58542926 influences hepatic fibrosis progression in patients with non-alcoholic fatty liver disease. Nat Commun, 2014, 5: 4309.
4. Coppola N, Rosa Z, Cirillo G, et al. TM6SF2 E167K variant is associated with severe steatosis in chronic hepatitis C, regardless of PNPLA3 polymorphism. Liver Int, 2015, 35(8): 1959-1963.
5. Dongiovanni P, Petta S, Maglio C, et al. Transmembrane 6 superfamily member 2 gene variant disentangles nonalcoholic steatohepatitis from cardiovascular disease. Hepatology, 2015, 61(2): 506-514.
6. Pietiainen V, Lindgren CM, Stefansson K, et al. TM6SF2 Glu167Lys polymorphism is associated with low levels of LDL-cholesterol and increased liver injury in obese children. Pediatr Obes, 2016, 11(2): 115-119.
7. Petta S, Maida M, Grimaudo 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, 2016, 36(2): 198-204.
8. Milano M, Aghemo A, Dongiovanni P, et al. Transmembrane 6 superfamily member 2 gene E167K variant impacts on steatosis and liver damage in chronic hepatitis C patients. Hepatology, 2015, 62(1): 111-117.
9. Sookoian S, Castano GO, Scian R, et al. Genetic variation in transmembrane 6 superfamily member 2 and the risk of nonalcoholic fatty liver disease and histological disease severity. Hepatology, 2015, 61(2): 515-525.
10. Goffredo M, Caprio S, Feldstein AE, et al. Role of the TM6SF2 rs58542926 in the pathogenesis of non-alcoholic pediatric fatty liver disease (NAFLD): A multiethnic study. Hepatology, 2016, 63(1): 117-125.
11. Scorletti E, West AL, Bhatia L, et al. Treating liver fat and serum triglyceride levels in NAFLD, effects of PNPLA3 and TM6SF2 genotypes: Results from the WELCOME trial. J Hepatol, 2015, 63(6): 1476-1483.
12. Mancina RM, Matikainen N, Maglio C, et al. Paradoxical dissociation between hepatic fat content and de novo lipogenesis due to PNPLA3 sequence variant. J Clin Endocrinol Metab, 2015, 100(5): E821-825.
13. Kozlitina J, Smagris E, Stender S, et al. Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease. Nat Genet, 2014, 46(4): 352-356.
14. Wong VW, Wong GL, Tse CH, et al. Prevalence of the TM6SF2 variant and non-alcoholic fatty liver disease in Chinese. Hepatology, 2014, 61(3): 708-709.
15. Akuta N, Kawamura Y, Arase Y, et al. Relationships between Genetic Variations of PNPLA3, TM6SF2 and Histological Features of Nonalcoholic Fatty Liver Disease in Japan. Gut Liver, 2016, 10(3): 437-445.
16. Arslanow A, Stokes CS, Weber SN, et al. The common PNPLA3 variant p.I148M is associated with liver fat contents as quantified by controlled attenuation parameter (CAP). Liver Int, 2016, 36(3): 418-426.

Chinese Journal of Evidence-Based Medicine

Association between the Polymorphism of the TM6SF2- rs58542926 Gene and Liver Damage and the Severity of Liver Fibrosis: A Meta-analysis

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