Vitamin D status and associated genetic polymorphisms in a cohort of UK children with non -alcoholic fatty liver disease

Background: Vitamin D deficiency has been associated with non-alcoholic fatty liver disease (NAFLD). However, the role of polymorphisms determining vitamin D status remains unknown. Objectives: To determine in UK children with biopsy-proven NAFLD: (i) vitamin D status throughout a 12-month period; (ii) interactions between key vitamin D-related genetic variants (NADSYN1/DHCR7, VDR, GC, CYP2R1) and disease severity. Methods: In 103 pediatric patients with NAFLD, serum 25-hydroxyvitamin D (25OHD) levels and genotypes were determined contemporaneously to liver biopsy, and examined in relation to NAFLD activity score and fibrosis stage. Results: Only 19.2% of children had adequate vitamin D status; most had mean 25OHD levels considered deficient (<25nmol/l, 25.5%) or insufficient (<50nmol/l, 55.3%). Patients had significantly lower 25OHD levels in winter months (95%CI: 22.7-31.2nmol/l) when compared to spring (30.5-42.1nmol/l; P=0.0089), summer (36.3-47.2nmol/l; P<0.0001) and autumn (34.2-47.5nmol/l; P=0.0003). Polymorphisms in the NADSYN1/DHCR7 (rs3829251, rs12785878), and VDR (rs2228570) genes were independently associated with increased steatosis; while a GC variant (rs4588) was associated with increased inflammation in liver biopsies. Conclusions: Children with NAFLD in the UK have particularly low winter vitamin D status; with vitamin D insufficiency prevalent throughout the year. Polymorphisms in the vitamin D metabolic pathway are associated with histological severity of pediatric NAFLD.