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Liver Int. 2018 Dec;38(12):2301-2308. doi: 10.1111/liv.13955. Epub 2018 Sep 25.

Relationship between non-alcoholic steatohepatitis, PNPLA3 I148M genotype and bone mineral density in adolescents.

Author information

1
Hepatology, Gastroenterology and Nutrition Unit, IRCCS "Bambino Gesù" Children's Hospital, Rome, Italy.
2
Endocrinology Unit, Pediatric University Department, Bambino Gesù Children's Hospital, Research Institute, Rome, Italy.
3
Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
4
National Institute for Health Research Southampton Biomedical Research Centre University of Southampton, University Hospital Southampton National Health Service (NHS) Foundation Trust, Southampton, UK.
5
Department of Pediatric, University "La Sapienza", Rome, Italy.

Abstract

BACKGROUND & AIMS:

It is uncertain whether non-alcoholic steatohepatitis (NASH) is a risk factor for low bone mineral density (BMD). Our aim was to investigate: (a) associations between NASH and BMD values and (b) associations between PNPLA3 I148M genotypes and BMD, in children with histologically proven non-alcoholic fatty liver disease (NAFLD).

METHODS:

BMD area (g/cm2 ) was measured using dual-energy X-ray absorptiometry (DEXA). NASH was diagnosed by a Steatosis, Activity and Fibrosis (SAF) score and FLIP algorithm. Genotyping for patatin-like phospholipase domain containing-3 (PNPLA3) I148M genotype (rs738409) (CC, CG and GG) was undertaken using the TaqMan SNP genotyping allelic discrimination method. Logistic regression was used to test associations [OR (95% CIs)] between low BMD, and both NASH and PNPLA3 I148M genotypes.

RESULTS:

Thirty-four adolescents (mean age 13.8 ± 1.1 years) with histologically confirmed NAFLD were studied. Subjects with NASH (n = 25) had a lower BMD (means (SDs) 0.87 ± 0.06 vs 0.97 ± 0.12, P = 0.005), compared to subjects without NASH. Subjects with PNPLA3 CG+GG genotypes had a lower BMD compared with subjects with PNPLA3-CC genotype (means (SDs) 0.79 ± 0.20 vs 0.92 ± 0.10, P = 0.009). PNPLA3 CG+GG genotypes were independently associated with NASH [OR (95% CIs 1.78, 1.24, 2.99)], and low BMD was associated with both PNPLA3 CG+GG (OR 3.62 (95% CIs 1.21, 5.53), P = 0.028) and with SAF score (OR 2.76 (95% CIs 1.12, 5.41), P = 0.045).

CONCLUSIONS:

Taken together the independent associations between: (a) low BMD and PNPLA3 CG+GG genotype; (b) low BMD and NASH; and (c) PNPLA3 CG+GG genotype and NASH, provide support for a causal relationship between NASH and low BMD.

KEYWORDS:

BMD; NASH; PNPLA3; children

PMID:
30176114
DOI:
10.1111/liv.13955
[Indexed for MEDLINE]

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