Xu Ke, Zheng Kenneth I, Zhu Pei-Wu, Liu Wen-Yue, Ma Hong-Lei, Li Gang, Tang Liang-Jie, Rios Rafael S, Targher Giovanni, Byrne Christopher D, Wang Xiao-Dong, Chen Yong-Ping, Zheng Ming-Hua
NAFLD Research Center, Department of Hepatology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
J Clin Transl Hepatol. 2022 Apr 28;10(2):219-229. doi: 10.14218/JCTH.2021.00067. Epub 2021 Jul 29.
Previous studies have reported that the single nucleotide polymorphisms (SNPs) of and 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 severity. We assessed the effect of these three SNPs on nonalcoholic steatohepatitis (NASH) and also examined the gene-gene interactions in a Chinese population with biopsy-confirmed NAFLD.
We enrolled 415 consecutive adult individuals with biopsy-proven NAFLD. Multivariable logistic regression analysis was undertaken to test associations between NASH and SNPs in and . Gene-gene interactions were analyzed by performing a generalized multifactor dimensionality reduction (GMDR) analysis.
The mean ± standard deviation age of these 415 patients was 41.3±12.5 years, and 75.9% were men. Patients with TT, AA or 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 predicting 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.
NAFLD patients carrying the TT, AA or GG genotypes are at greater risk of NASH. These three SNPs may synergistically interact to increase susceptibility to NASH.
既往研究报道，[基因名称1]和[基因名称2]的单核苷酸多态性（SNP）与非酒精性脂肪性肝病（NAFLD）相关。然而，尚无研究探讨这三种基因型之间的相互作用对肝脏疾病严重程度的影响。我们评估了这三种SNP对非酒精性脂肪性肝炎（NASH）的影响，并在经活检确诊为NAFLD的中国人群中研究了基因-基因相互作用。
我们纳入了415例经活检证实为NAFLD的连续成年个体。采用多变量逻辑回归分析来检验NASH与[基因名称1]和[基因名称2]中SNP之间的关联。通过进行广义多因素降维（GMDR）分析来分析基因-基因相互作用。
这415例患者的平均年龄±标准差为41.3±12.5岁，男性占75.9%。即使在调整年龄、性别和体重指数后，携带[基因名称1]TT、[基因名称2]AA或[基因名称3]GG基因型的患者发生NASH的风险更高。GMDR分析表明，所有三种SNP的组合是预测NASH的最佳模型。此外，预测NASH风险的单倍型T-A-G的优势比几乎是单倍型G-C-C的三倍。
携带[基因名称1]TT、[基因名称2]AA或[基因名称3]GG基因型的NAFLD患者发生NASH的风险更高。这三种SNP可能协同相互作用，增加对NASH的易感性。
