Association of chitotriosidase genotype with the development of non-alcoholic fatty liver disease

Aim: 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. Methods: We genotyped 200 patients with NAFLD (110 with non-alcoholic steatohepatitis [NASH] and 90 with simple steatosis) and 100 control subjects. The 2-test was performed for a casecontrol 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. Results: 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. Conclusion: These findings suggest that a functional polymorphism in the CHIT-1 gene protects against NAFLD progression.