Variants in the UGT1A1 gene and the risk of pediatric nonalcoholic fatty liver disease

Abstract

Objective: Oxidative stress is increased in nonalcoholic fatty liver disease (NAFLD). Variants in the UGT1A1 gene contribute to increased bilirubin levels, and bilirubin can act as an antioxidant. We hypothesize that variant UGT1A1 genotypes reduce the risk for NAFLD development.

Methods: Two hundred thirty-four obese children 6 to 13 years of age were recruited. NAFLD was determined through liver ultrasonography. The UGT1A1 genotypes UGT1A1*6 and UGT1A1*28 were detected. We assessed the effects of UGT1A1 genotypes on pediatric NAFLD.

Results: In total, 12% of the obese children had NAFLD. The subjects with NAFLD had lower serum total bilirubin levels (0.25 +/- 0.30 mg/dL) than did those without NAFLD (0.36 +/- 0.38 mg/dL; P = .021). With conditioning on the effects of age- and gender-adjusted BMI, waist/hip ratio, and adiponectin levels, variant UGT1A1*6 genotypes were a protecting factor for NAFLD, with an estimated adjusted odds ratio of 0.31 (95% confidence interval: 0.11-0.91; P = .033), but variant UGT1A1*28 genotypes were not significantly associated with the occurrence of NAFLD.

Conclusions: Variant UGT1A1*6 genotypes are associated with a lower risk of NAFLD in obese Taiwanese children. The UGT1A1 genotype is a new risk factor for pediatric NAFLD.