首页|Interaction of SAMM50-rs738491, PARVB-rs5764455 and PNPLA3-rs738409 Increases Susceptibility to Nonalcoholic Steatohepatitis

Interaction of SAMM50-rs738491, PARVB-rs5764455 and PNPLA3-rs738409 Increases Susceptibility to Nonalcoholic Steatohepatitis

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Background and Aims: Previous studies have reported that the single nucleotide polymorphisms (SNPs) of SAMM50-rs738491, PARVB-rs5764455 and PNPLA3-rs738409 are associated with nonalcoholic fatty liver disease (NAFLD). However, no studies have examined the effect of interactions between these three genotypes to affect liver disease severi-ty. We assessed the effect of these three SNPs on nonalcohol-ic steatohepatitis (NASH) and also examined the gene-gene interactions in a Chinese population with biopsy-confirmed NAFLD. Methods: We enrolled 415 consecutive adult individ-uals with biopsy-proven NAFLD. Multivariable logistic regres-sion analysis was undertaken to test associations between NASH and SNPs in SAMM50-rs738491, PARVB-rs5764455 and PNPLA3-rs738409. Gene-gene interactions were ana-lyzed by performing a generalized multifactor dimensionality reduction (GMDR) analysis. Results: The mean ± standard deviation age of these 415 patients was 41.3±12.5 years, and 75.9％ were men. Patients with SAMM50-rs738491 TT, PARVB-rs5764455 AA or PNPLA3-rs738409 GG genotypes had a higher risk of NASH, even after adjustment for age, sex and body mass index. GMDR analysis showed that the combination of all three SNPs was the best model for predict-ing NASH. Additionally, the odds ratio of the haplotype T-A-G for predicting the risk of NASH was nearly three times higher than that of the haplotype G-C-C. Conclusions: NAFLD pa-tients carrying the SAMM50-rs738491 TT, PARVB-rs5764455 AA or PNPLA3-rs738409 GG genotypes are at greater risk of NASH. These three SNPs may synergistically interact to increase susceptibility to NASH.

Gene polymorphismsGene-gene interactionSAMM50PARVBPNPLA3NASH

Ke Xu、Kenneth I.Zheng、Pei-Wu Zhu、Wen-Yue Liu、Hong-Lei Ma、Gang Li、Liang-Jie Tang、Rafael S.Rios、Giovanni Targher、Christopher D.Byrne、Xiao-Dong Wang、Yong-Ping Chen、Ming-Hua Zheng

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NAFLD Research Center,Department of Hepatology,First Affiliated Hospital of Wenzhou Medical University,Wenzhou,Zhe-jiang,China

Department of Thoracic Surgery,Shanghai Chest Hospital,Shanghai Jiao Tong University,Shanghai,China

Department of Laboratory Medicine,First Affiliated Hospital of Wenzhou Medical University,Wenzhou,Zhejiang,China

Department of Endocrinology,First Affiliated Hospital of Wenzhou Medical University,Wenzhou,Zhejiang,China

Section of Endocrinology,Diabetes and Metabolism,Department of Medicine,University and Azienda Ospedaliera Universitaria In-tegrata of Verona,Verona,Italy

Southampton National Institute for Health Research Biomedical Research Centre,Univer-sity Hospital Southampton,Southampton General Hospital,Southampton,UK

Institute of Hepatology,Wenzhou Medical University,Wenzhou,Zhejiang,China

Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease in Zhejiang Province,Wenzhou,Zhejiang,China

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国家自然科学基金High Level Creative Talents from Department of Public Health in Zhejiang ProvinceProject of New Century 551 Talent Nurturing in WenzhouSchool of Medicine,University of Verona,Verona,ItalySouthampton NIHR Biomedical Research Centre,UK

82070588S2032102600032ISBRC-20004

2022

10.14218/JCTH.2021.00067

临床与转化肝病杂志(英文版)

临床与转化肝病杂志(英文版)

ISSN：
年,卷(期)：2022.10(2)
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