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Linked PNPLA3 polymorphisms confer susceptibility to nonalcoholic steatohepatitis and decreased viral load in chronic hepatitis B.
World J Gastroenterol 2015; 21(28):8605-14WJ

Abstract

AIM

To investigate the association of PNPLA3 polymorphisms with concurrent chronic hepatitis B (CHB) and nonalcoholic fatty liver disease (NAFLD).

METHODS

A cohort of Han patients with biopsy-proven CHB, with or without NAFLD (CHB group, n = 51; CHB + NAFLD group, n = 57), and normal controls (normal group, n = 47) were recruited from Northern (Tianjin), Central (Shanghai), and Southern (Zhangzhou) China. Their PNPLA3 polymorphisms were genotyped by gene sequencing. The association between PNPLA3 polymorphisms and susceptibility to NAFLD, and clinical characteristics of NAFLD were evaluated on the basis of physical indices, liver function tests, glycolipid metabolism, and histopathologic scoring. The association of PNPLA3 polymorphisms and hepatitis B virus (HBV) load was determined by the serum level of HBV DNA.

RESULTS

After adjusting for age, sex, and body mass index, we found that four linked single nucleotide polymorphisms (SNPs) of PNPLA3, including the rs738409 G allele (CHB + NAFLD group vs CHB group: odds ratio [OR] = 2.77, 95% confidence interval [CI]: 1.18-6.54; P = 0.02), rs3747206 T allele (CHB + NAFLD group vs CHB group: OR = 2.77, 95%CI: 1.18-6.54; P = 0.02), rs4823173 A allele (CHB + NAFLD group vs CHB group: OR = 2.73, 95%CI: 1.16-6.44; P = 0.02), and rs2072906 G allele (CHB + NAFLD group vs CHB group: OR = 3.05, 95%CI: 1.28-7.26; P = 0.01), conferred high risk to NAFLD in CHB patients. In patients with both CHB and NAFLD, these genotypes of PNPLA3 polymorphisms were associated with increased susceptibility to nonalcoholic steatohepatitis (NASH) (NAFLD activity score ≥ 3; P = 0.01-0.03) and liver fibrosis (> 1 Metavir grading; P = 0.01-0.04). As compared to those with C/C and C/G at rs738409, C/C and C/T at rs3747206, G/G and G/A at rs4823173, and A/A and A/G at rs2072906, patients in the CHB + NAFLD group with G/G at rs738409, T/T at rs3747206, A/A at rs4823173, and G/G at rs2072906 showed significantly lower serum levels of HBV DNA (P < 0.01-0.05).

CONCLUSION

Four linked SNPs of PNPLA3 (rs738409, rs3747206, rs4823173, and rs2072906) are correlated with susceptibility to NAFLD, NASH, liver fibrosis, and HBV dynamics in CHB patients.

Authors+Show Affiliations

Qin Pan, Rui-Nan Zhang, Yu-Qin Wang, Feng Shen, Jia-Fa Lu, Chan-Yan Zhu, Shu-Yi Zhang, Yi-Ming Chen, Wan-Lu Sun, Jian-Gao Fan, Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.Qin Pan, Rui-Nan Zhang, Yu-Qin Wang, Feng Shen, Jia-Fa Lu, Chan-Yan Zhu, Shu-Yi Zhang, Yi-Ming Chen, Wan-Lu Sun, Jian-Gao Fan, Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.Qin Pan, Rui-Nan Zhang, Yu-Qin Wang, Feng Shen, Jia-Fa Lu, Chan-Yan Zhu, Shu-Yi Zhang, Yi-Ming Chen, Wan-Lu Sun, Jian-Gao Fan, Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.Qin Pan, Rui-Nan Zhang, Yu-Qin Wang, Feng Shen, Jia-Fa Lu, Chan-Yan Zhu, Shu-Yi Zhang, Yi-Ming Chen, Wan-Lu Sun, Jian-Gao Fan, Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.Qin Pan, Rui-Nan Zhang, Yu-Qin Wang, Feng Shen, Jia-Fa Lu, Chan-Yan Zhu, Shu-Yi Zhang, Yi-Ming Chen, Wan-Lu Sun, Jian-Gao Fan, Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.Qin Pan, Rui-Nan Zhang, Yu-Qin Wang, Feng Shen, Jia-Fa Lu, Chan-Yan Zhu, Shu-Yi Zhang, Yi-Ming Chen, Wan-Lu Sun, Jian-Gao Fan, Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.Qin Pan, Rui-Nan Zhang, Yu-Qin Wang, Feng Shen, Jia-Fa Lu, Chan-Yan Zhu, Shu-Yi Zhang, Yi-Ming Chen, Wan-Lu Sun, Jian-Gao Fan, Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.Qin Pan, Rui-Nan Zhang, Yu-Qin Wang, Feng Shen, Jia-Fa Lu, Chan-Yan Zhu, Shu-Yi Zhang, Yi-Ming Chen, Wan-Lu Sun, Jian-Gao Fan, Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.Qin Pan, Rui-Nan Zhang, Yu-Qin Wang, Feng Shen, Jia-Fa Lu, Chan-Yan Zhu, Shu-Yi Zhang, Yi-Ming Chen, Wan-Lu Sun, Jian-Gao Fan, Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.Qin Pan, Rui-Nan Zhang, Yu-Qin Wang, Feng Shen, Jia-Fa Lu, Chan-Yan Zhu, Shu-Yi Zhang, Yi-Ming Chen, Wan-Lu Sun, Jian-Gao Fan, Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.Qin Pan, Rui-Nan Zhang, Yu-Qin Wang, Feng Shen, Jia-Fa Lu, Chan-Yan Zhu, Shu-Yi Zhang, Yi-Ming Chen, Wan-Lu Sun, Jian-Gao Fan, Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.Qin Pan, Rui-Nan Zhang, Yu-Qin Wang, Feng Shen, Jia-Fa Lu, Chan-Yan Zhu, Shu-Yi Zhang, Yi-Ming Chen, Wan-Lu Sun, Jian-Gao Fan, Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.Qin Pan, Rui-Nan Zhang, Yu-Qin Wang, Feng Shen, Jia-Fa Lu, Chan-Yan Zhu, Shu-Yi Zhang, Yi-Ming Chen, Wan-Lu Sun, Jian-Gao Fan, Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.Qin Pan, Rui-Nan Zhang, Yu-Qin Wang, Feng Shen, Jia-Fa Lu, Chan-Yan Zhu, Shu-Yi Zhang, Yi-Ming Chen, Wan-Lu Sun, Jian-Gao Fan, Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26229402

Citation

Pan, Qin, et al. "Linked PNPLA3 Polymorphisms Confer Susceptibility to Nonalcoholic Steatohepatitis and Decreased Viral Load in Chronic Hepatitis B." World Journal of Gastroenterology, vol. 21, no. 28, 2015, pp. 8605-14.
Pan Q, Zhang RN, Wang YQ, et al. Linked PNPLA3 polymorphisms confer susceptibility to nonalcoholic steatohepatitis and decreased viral load in chronic hepatitis B. World J Gastroenterol. 2015;21(28):8605-14.
Pan, Q., Zhang, R. N., Wang, Y. Q., Zheng, R. D., Mi, Y. Q., Liu, W. B., ... Fan, J. G. (2015). Linked PNPLA3 polymorphisms confer susceptibility to nonalcoholic steatohepatitis and decreased viral load in chronic hepatitis B. World Journal of Gastroenterology, 21(28), pp. 8605-14. doi:10.3748/wjg.v21.i28.8605.
Pan Q, et al. Linked PNPLA3 Polymorphisms Confer Susceptibility to Nonalcoholic Steatohepatitis and Decreased Viral Load in Chronic Hepatitis B. World J Gastroenterol. 2015 Jul 28;21(28):8605-14. PubMed PMID: 26229402.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Linked PNPLA3 polymorphisms confer susceptibility to nonalcoholic steatohepatitis and decreased viral load in chronic hepatitis B. AU - Pan,Qin, AU - Zhang,Rui-Nan, AU - Wang,Yu-Qin, AU - Zheng,Rui-Dan, AU - Mi,Yu-Qiang, AU - Liu,Wen-Bin, AU - Shen,Feng, AU - Chen,Guang-Yu, AU - Lu,Jia-Fa, AU - Zhu,Chan-Yan, AU - Zhang,Shu-Yi, AU - Chen,Yi-Ming, AU - Sun,Wan-Lu, AU - Fan,Jian-Gao, PY - 2015/01/23/received PY - 2015/03/05/revised PY - 2015/04/16/accepted PY - 2015/8/1/entrez PY - 2015/8/1/pubmed PY - 2016/3/16/medline KW - Chronic hepatitis B KW - Hepatitis B virus KW - Nonalcoholic fatty liver disease KW - PNPLA3 KW - Single-nucleotide polymorphism SP - 8605 EP - 14 JF - World journal of gastroenterology JO - World J. Gastroenterol. VL - 21 IS - 28 N2 - AIM: To investigate the association of PNPLA3 polymorphisms with concurrent chronic hepatitis B (CHB) and nonalcoholic fatty liver disease (NAFLD). METHODS: A cohort of Han patients with biopsy-proven CHB, with or without NAFLD (CHB group, n = 51; CHB + NAFLD group, n = 57), and normal controls (normal group, n = 47) were recruited from Northern (Tianjin), Central (Shanghai), and Southern (Zhangzhou) China. Their PNPLA3 polymorphisms were genotyped by gene sequencing. The association between PNPLA3 polymorphisms and susceptibility to NAFLD, and clinical characteristics of NAFLD were evaluated on the basis of physical indices, liver function tests, glycolipid metabolism, and histopathologic scoring. The association of PNPLA3 polymorphisms and hepatitis B virus (HBV) load was determined by the serum level of HBV DNA. RESULTS: After adjusting for age, sex, and body mass index, we found that four linked single nucleotide polymorphisms (SNPs) of PNPLA3, including the rs738409 G allele (CHB + NAFLD group vs CHB group: odds ratio [OR] = 2.77, 95% confidence interval [CI]: 1.18-6.54; P = 0.02), rs3747206 T allele (CHB + NAFLD group vs CHB group: OR = 2.77, 95%CI: 1.18-6.54; P = 0.02), rs4823173 A allele (CHB + NAFLD group vs CHB group: OR = 2.73, 95%CI: 1.16-6.44; P = 0.02), and rs2072906 G allele (CHB + NAFLD group vs CHB group: OR = 3.05, 95%CI: 1.28-7.26; P = 0.01), conferred high risk to NAFLD in CHB patients. In patients with both CHB and NAFLD, these genotypes of PNPLA3 polymorphisms were associated with increased susceptibility to nonalcoholic steatohepatitis (NASH) (NAFLD activity score ≥ 3; P = 0.01-0.03) and liver fibrosis (> 1 Metavir grading; P = 0.01-0.04). As compared to those with C/C and C/G at rs738409, C/C and C/T at rs3747206, G/G and G/A at rs4823173, and A/A and A/G at rs2072906, patients in the CHB + NAFLD group with G/G at rs738409, T/T at rs3747206, A/A at rs4823173, and G/G at rs2072906 showed significantly lower serum levels of HBV DNA (P < 0.01-0.05). CONCLUSION: Four linked SNPs of PNPLA3 (rs738409, rs3747206, rs4823173, and rs2072906) are correlated with susceptibility to NAFLD, NASH, liver fibrosis, and HBV dynamics in CHB patients. SN - 2219-2840 UR - https://www.unboundmedicine.com/medline/citation/26229402/Linked_PNPLA3_polymorphisms_confer_susceptibility_to_nonalcoholic_steatohepatitis_and_decreased_viral_load_in_chronic_hepatitis_B_ L2 - http://www.wjgnet.com/1007-9327/full/v21/i28/8605.htm DB - PRIME DP - Unbound Medicine ER -