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, 13 (7), 433-441

Vitamin D Status and Associated Genetic Polymorphisms in a Cohort of UK Children With Non-Alcoholic Fatty Liver Disease

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Vitamin D Status and Associated Genetic Polymorphisms in a Cohort of UK Children With Non-Alcoholic Fatty Liver Disease

P S Gibson et al. Pediatr Obes.

Abstract

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: The objectives of this study were to determine in UK children with biopsy-proven NAFLD (i) their vitamin D status throughout a 12-month period and (ii) interactions between key vitamin D-related genetic variants (nicotinamide adenine dinucleotide synthase-1/dehydrocholesterol reductase-7, vitamin D receptor, group-specific component, CYP2R1) and disease severity.

Methods: In 103 paediatric 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 (<25 nmol·L-1 , 25.5%) or insufficient (<50 nmol·L-1 , 55.3%). Patients had significantly lower 25OHD levels in winter months (95% CI: 22.7-31.2 nmol·L-1 ) when compared with spring (30.5-42.1 nmol·L-1 ; P = 0.0089), summer (36.3-47.2 nmol·L-1 ; P < 0.0001) and autumn (34.2-47.5 nmol·L-1 ; P = 0.0003). Polymorphisms in the nicotinamide adenine dinucleotide synthase-1/dehydrocholesterol reductase-7 (rs3829251, rs12785878) and vitamin D receptor (rs2228570) genes were independently associated with increased steatosis; while a group-specific component 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 paediatric NAFLD.

Keywords: 25OHD; genotype; non-alcoholic fatty liver disease; vitamin D.

Figures

Figure 1
Figure 1
Serum 25OHD levels and histological grading. (a) Independent and repeated measures of serum 25OHD levels of cohort. Dashed lines shows accepted thresholds for deficiency (red) and insufficiency (green). (b) In Caucasian patients, Brunt/Kleiner NAS grading vs. predicted August 25OHD status demonstrates lower levels in patients with more severe disease using standard cut‐offs for simple steatosis (score 0–2), Borderline NASH (3–4) and NASH (5–8). (c) Utilizing a score of <5 and ≥5 to define severity of disease, those with less severe disease had significantly lower 25OHD in the group as a whole, with a similar trend in Caucasian patients only (d). Fibrosis grading vs. predicted August 25OHD status in all patients (e) and Caucasian patients (f) are shown. 25OHD levels are expressed around the mean ± 95% CI; data were tested for normality using the D'Agostino and Pearson omnibus normality test and analysed using an unpaired t‐test. 25OHD, 25‐hydroxyvitamin D; NASH, nonalcoholic steatohepatitis.
Figure 2
Figure 2
Histological scoring for steatosis in Caucasian patients in relationship to genotype for (a) PNPLA3 rs738409, (b) NADYSN1/DHCR7 rs12785878, (c) NADSYN1/DHCR7 rs3829251 and (d) VDR rs2228570. Histological scoring for inflammation in the same population in relationship to genotype for (e) PNPLA3 and (f) GC rs4588. All data are representative of population percentages and were assessed by chi‐squared test. DHCR7, dehydrocholesterol reductase‐7; GC, group‐specific component; NADSYN1, nicotinamide adenine dinucleotide synthase‐1; PNPLA3, patatin‐like phospholipase domain‐containing protein 3; VDR, vitamin D receptor.

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References

    1. Giorgio V, Prono F, Graziano F, Nobili V. Pediatric non alcoholic fatty liver disease: old and new concepts on development, progression, metabolic insight and potential treatment targets. BMC Pediatr 2013; 13: 40. - PMC - PubMed
    1. Brunt EM, Kleiner DE, Wilson LA, et al Portal chronic inflammation in nonalcoholic fatty liver disease (NAFLD): a histologic marker of advanced NAFLD‐Clinicopathologic correlations from the nonalcoholic steatohepatitis clinical research network. Hepatology 2009; 49: 809–820. - PMC - PubMed
    1. Moore JB. Non‐alcoholic fatty liver disease: the hepatic consequence of obesity and the metabolic syndrome. Proc Nutr Soc 2010; 69: 211–220. - PubMed
    1. Chalasani N, Younossi Z, Lavine JE, et al The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology 2017; 67: 328–357. - PubMed
    1. Black LJ, Jacoby P, She Ping‐Delfos WC, et al Low serum 25‐hydroxyvitamin D concentrations associate with non‐alcoholic fatty liver disease in adolescents independent of adiposity. J Gastroenterol Hepatol 2014; 29: 1215–1222. - PubMed

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