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

Abstract

Background and 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 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

34 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) v. 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 v. 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.

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Identifiers

ORCID for Christopher Byrne: orcid.org/0000-0001-6322-7753

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