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Parental History of Type 2 Diabetes Mellitus and PNPLA3 Polymorphism Increase the Risk of Severe Stages of Nonalcoholic Fatty Liver Disease

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Abstract

Background & Aims

In non-alcoholic fatty liver disease (NAFLD), the influence of parental history of type 2 diabetes (T2D) allied to single nucleotide polymorphisms (SNPs) in the offspring is not known. We aimed to investigate the impact of the parental history of T2D, PNPLA3 and TM6SF2 polymorphisms in liver steatosis and fibrosis.

Methods

This was a case–control study involving the offspring of T2D patients and controls without a parental history of T2D. Participants underwent clinical and laboratory evaluation, transient elastography (TE) by Fibroscan® (Echosens, Fr) and genotyping for PNPLA3 and TM6SF2. Multivariate logistic regression evaluated the influence of parental history of T2D on liver steatosis and fibrosis, controlled for age, gender, metabolic traits and SNPs.

Results

161 T2D offspring and 78 controls, 10–46 years old, were included. The offspring of T2D had higher prevalences of obesity, T2D, arterial hypertension and sedentarism. Parental history of T2D was associated with fibrosis ≥ F2 (OR 8.89, CI 95% 1.09–72.01, p = 0.041) after adjustment for age, gender, metabolic traits and SNPs. PNPLA3 GG genotype was independently associated with steatosis ≥ S1 (OR 8.15, CI 95% 1.93–34.38, p = 0.004) and fibrosis ≥ F2 (OR 4.31, CI 95% 1.11–16.61, p = 0.034).

Conclusions

The offspring of T2D patients present a worse metabolic profile and the parental history of T2D confers an increased likelihood of hepatic fibrosis, independent of metabolic factors. PNPLA3 homozygous GG, but not TM6SF2 genotypes, also impacts on this phenotype.

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Abbreviations

NAFLD:

Non-alcoholic fatty liver disease

T2D:

Type 2 Diabetes

NASH:

Non-alcoholic steatohepatitis

PNPLA3 :

Patatin-like phospholipase domain containing 3

TM6SF2 :

Transmembrane 6 superfamily member 2

SNP:

Single nucleotide polymorphism

TE:

Transient elastography

CAP:

Controlled attenuation parameter

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Funding

This study was supported by grants from Brazilian National Council for Scientifical and Technological Development (CNPq-Brazil). Grant number 311714/2018-8.

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Authors and Affiliations

  1. Division of Hepatology, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rua Professor Rodolpho Paulo Rocco, 255- Cidade Universitária, Rio de Janeiro, RJ, 20941-913, Brazil

    Natalia Balassiano Wajsbrot & Nathalie Carvalho Leite

  2. Post-Graduation Program On Health and Environment, University of the Region of Joinville (Univille), Santa Catarina, Brazil

    Paulo Henrique Condeixa Franca

  3. Department of Internal Medicine, Medical School, Federal University of Rio de Janeiro, Rio de Janeiro, 20941-913, Brazil

    Claudia Regina Lopes Cardoso, Gil Fernando Salles & Cristiane A. Villela-Nogueira

Authors
  1. Natalia Balassiano Wajsbrot
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  2. Nathalie Carvalho Leite
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  3. Paulo Henrique Condeixa Franca
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  4. Claudia Regina Lopes Cardoso
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  5. Gil Fernando Salles
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  6. Cristiane A. Villela-Nogueira
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Contributions

Nathalie C. Leite, Gil F. Salles and Cristiane A. Villela-Nogueira contributed to the study design and critical revision of the manuscript; all authors contributed to data analysis, writing the initial draft and approved the final version to be published.

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Correspondence to Natalia Balassiano Wajsbrot.

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Wajsbrot, N.B., Leite, N.C., Franca, P.H.C. et al. Parental History of Type 2 Diabetes Mellitus and PNPLA3 Polymorphism Increase the Risk of Severe Stages of Nonalcoholic Fatty Liver Disease. Dig Dis Sci 69, 634–642 (2024). https://doi.org/10.1007/s10620-023-08214-7

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  • DOI: https://doi.org/10.1007/s10620-023-08214-7

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