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1 "Rosalba Minisini"
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Original Article
Genetics
Severity of Nonalcoholic Fatty Liver Disease in Type 2 Diabetes Mellitus: Relationship between Nongenetic Factors and PNPLA3/HSD17B13 Polymorphisms
Mattia Bellan, Cosimo Colletta, Matteo Nazzareno Barbaglia, Livia Salmi, Roberto Clerici, Venkata Ramana Mallela, Luigi Mario Castello, Giuseppe Saglietti, Gian Piero Carnevale Schianca, Rosalba Minisini, Mario Pirisi
Diabetes Metab J. 2019;43(5):700-710.   Published online July 29, 2019
DOI: https://doi.org/10.4093/dmj.2018.0201
  • 4,900 View
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  • 16 Web of Science
  • 17 Crossref
AbstractAbstract PDFPubReader   
Background

The prevalence of nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM) is high, though its severity is often underestimated. Our aim is to provide an estimate of the prevalence of severe NAFLD in T2DM and identify its major predictors.

Methods

T2DM patients (n=328) not previously known to have NAFLD underwent clinical assessment, transient elastography with measure of liver stiffness (LS) and controlled attenuation parameter (CAP), and genotyping for patatin like phospholipase domain containing 3 (PNPLA3) and 17β-hydroxysteroid-dehydrogenase type 13 (HSD17B13).

Results

Median LS was 6.1 kPa (4.9 to 8.6). More than one-fourth patients had advanced liver disease, defined as LS ≥7.9 kPa (n=94/238, 29%), and had a higher body mass index (BMI) than those with a LS <7.9 kPa. Carriage of the G allele in the PNPLA3 gene was associated with higher LS, being 5.9 kPa (4.7 to 7.7) in C/C homozygotes, 6.1 kPa (5.2 to 8.7) in C/G heterozygotes, and 6.8 kPa (5.8 to 9.2) in G/G homozygotes (P=0.01). This trend was absent in patients with ≥1 mutated HSD17B13 allele. In a multiple linear regression model, BMI and PNPLA3 genotype predicted LS, while age, gender, disease duration, and glycosylated hemoglobin did not fit into the model. None of these variables was confirmed to be predictive among carriers of at least one HSD17B13 mutated allele. There was no association between CAP and polymorphisms of PNPLA3 or HSD17B13.

Conclusion

Advanced NAFLD is common among T2DM patients. LS is predicted by both BMI and PNPLA3 polymorphism, the effect of the latter being modulated by mutated HSD17B13.

Citations

Citations to this article as recorded by  
  • miRNA and lncRNA as potential tissue biomarkers in hepatocellular carcinoma
    Venkata Ramana Mallela, Marie Rajtmajerová, Andriy Trailin, Václav Liška, Kari Hemminki, Filip Ambrozkiewicz
    Non-coding RNA Research.2024; 9(1): 24.     CrossRef
  • 17-Beta-Hydroxysteroid Dehydrogenase 13 Loss of Function Does Not Confer Protection to Nonalcoholic Fatty Liver Disease in Indian Population
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    Frontiers in Endocrinology.2023;[Epub]     CrossRef
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  • Interplay of PNPLA3 and HSD17B13 Variants in Modulating the Risk of Hepatocellular Carcinoma among Hepatitis C Patients
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Diabetes Metab J : Diabetes & Metabolism Journal