Department of Biomedical Sciences, University of Catania, Catania, Italy.
Hepatol Res. 2013 Mar;43(3):267-75. doi: 10.1111/j.1872-034X.2012.01063.x. Epub 2012 Sep 13.
Based on the role of chitotriosidase (CHIT-1) in the evolution of non-alcoholic fatty liver disease, we explored whether CHIT-1 mutant allele plays a role in NAFLD progression.
We genotyped 200 patients with NAFLD (110 with non-alcoholic steatohepatitis [NASH] and 90 with simple steatosis) and 100 control subjects. The χ(2) -test was performed for a case-control study. Odds ratios (OR) were adjusted for age, sex and body mass index (BMI) by using multiple logistic regression analysis with genotypes (additive model), age, sex and BMI as the independent variables. Multiple linear regression analysis was performed to test the independent effect of risk allele on clinical parameters while considering the effects of other variables (age, sex and BMI), which were assumed to be independent of the effect of the single nucleotide polymorphism.
The risk allele frequency of CHIT-1 wild type (Wt) was 0.71 in the control subjects, 0.77 in simple steatosis and 0.92 in patients with NASH. The OR (95% confidence interval) adjusted for age and BMI was 1.73. Multiple linear regression analysis indicated that the CHIT-1 Wt was significantly associated with increases in ferritin levels (P = 0.014) and the fibrosis stage (P = 0.011) in the patients with NASH, even after adjustment for age, sex and BMI, corroborating that the presence of the CHIT-1 Wt allele was an independent predictor of fibrotic NAFLD. In contrast, the steatosis grade was not associated with CHIT-1 mutant allele.
These findings suggest that a functional polymorphism in the CHIT-1 gene protects against NAFLD progression.
基于几丁质酶 1（CHIT-1）在非酒精性脂肪性肝病（NAFLD）进展中的作用，我们探讨 CHIT-1 突变等位基因是否在 NAFLD 进展中发挥作用。
我们对 200 例 NAFLD 患者（110 例非酒精性脂肪性肝炎[NASH]和 90 例单纯性脂肪变性）和 100 例对照进行基因分型。采用病例对照研究进行卡方检验。采用多因素逻辑回归分析，以基因型（加性模型）、年龄、性别和体重指数（BMI）为自变量，调整年龄、性别和 BMI，计算比值比（OR）。进行多元线性回归分析，以检验风险等位基因对临床参数的独立影响，同时考虑其他变量（年龄、性别和 BMI）的影响，假设这些变量与单核苷酸多态性的影响无关。
对照组 CHIT-1 野生型（Wt）等位基因频率为 0.71，单纯性脂肪变性为 0.77，NASH 患者为 0.92。调整年龄和 BMI 后，OR（95%可信区间）为 1.73。多元线性回归分析表明，在 NASH 患者中，CHIT-1 Wt 与铁蛋白水平升高（P = 0.014）和纤维化分期（P = 0.011）显著相关，即使在调整年龄、性别和 BMI 后，也证实 CHIT-1 Wt 等位基因的存在是纤维化 NAFLD 的独立预测因子。相反，脂肪变性程度与 CHIT-1 突变等位基因无关。
这些发现表明 CHIT-1 基因的功能多态性可预防 NAFLD 进展。
