Usefulness of <i>PNPLA3</i> variant for predicting hepatic events in steatotic liver disease: a matter of ethnicity or baseline risk?

Vespasiani‐Gentilucci, Umberto; Valenti, Luca; Romeo, Stefano

doi:10.1111/liv.15697

Cited by 5 publications

(3 citation statements)

References 29 publications

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“…44,45 While incorporating PNPLA3 genotyping into clinical practice seems promising, challenges including ethical considerations, cost-effectiveness, unclear improvement over existing methods (e.g., histological staging and non-invasive scores), and patient communication strategies need careful evaluation. 10 Further research is needed to address these challenges and provide a framework for potential clinical implementation. PNPLA3-environmental interactions contribute signi cantly to shaping the MASLD phenotype.…”

Section: Discussionmentioning

confidence: 99%

“…[5][6][7] In particular, the interplay of this genetic factor with both treatment and environmental factors has attracted considerable scienti c interest 8,9 in a discussion centered on the potential usefulness of PNPLA3 genotyping to guide MASLD management. 10 Despite these advances, the genetic epidemiology of PNPLA3 in MASLD patients and the extent of its impact on disease phenotype, as well as potential variations due to environmental factors, remain uncertain.…”

Section: Introductionmentioning

confidence: 99%

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Global epidemiology and implications of PNPLA3 I148M variant in MASLD: a systematic review and meta-analysis

Souza,

Al-Sharif,

Diaz

et al. 2024

Preprint

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Background and Aims: PNPLA3 rs738409 variant is a risk factor for onset and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to assess its global prevalence, clinical and histological characteristics, and long-term outcomes in patients with MASLD. Methods PubMed and Embase were searched until December 2023 for observational studies on PNPLA3 genotyped adults with MASLD. Proportions were pooled using a generalised linear mixed model with Clopper-Pearson intervals. Continuous and dichotomous variables were analysed using the DerSimonian-Laird method. Subgroup, meta-regression and sensitivity analyses were also performed. PROSPERO registration number: CRD42023449838. Results We identified 109 studies (118,302 MASLD individuals) with an overall minor allele frequency of the G allele at PNPLA3 [MAF(G)] of 0.45 (95%CI 0.43; 0.48, I²=98%), adjusted to 0.39 (95%CI 0.36; 0.43, I²=98%) due to publication bias. The highest MAF(G) was found in Latin America and the lowest in Europe. No African countries were identified. Carriers of the PNPLA3 variant had reduced adiposity, altered fat metabolism and worse liver damage/histology than non-carriers. Additionally, only the PNPLA3 GG genotype was associated with mortality and liver-related events. Meta-regressions showed the influence of adiposity, age, diabetes mellitus and glucose on PNPLA3 expression. Conclusions This study reveals the global pattern of PNPLA3 and its clinical, histological and outcomes implications in MASLD. Our findings underscore the importance of PNPLA3 genotyping in clinical trials and advocate for personalized medicine approaches. Further research is needed on the genetic epidemiology of underrepresented populations, challenges of incorporating genotyping into clinical practice and gene-environment interactions.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Global epidemiology and implications of PNPLA3 I148M variant in MASLD: a systematic review and meta-analysis

Souza,

Al-Sharif,

Diaz

et al. 2024

Preprint

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“…In this regard, men consume more alcohol and tobacco than women. For this reason, the male gender and an unhealthy lifestyle are risk factors linked to MASLD development [41] . Furthermore, a recent study showed that the number of alcoholic liver disease and MASLD-related deaths was higher in the white American population compared to the African American population during the 1999-2020 period [32] .…”

Section: Age Gender Tobacco Ethnicity and Genetic Factorsmentioning

confidence: 99%

Dysmetabolic comorbidities and non-alcoholic fatty liver disease: a stairway to metabolic dysfunction-associated steatotic liver disease

Colaci,

Gambardella,

Maria Scarlata

et al. 2024

Hepatoma Res

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Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. This term does not describe the pathogenetic mechanisms and complications associated with NAFLD. The new definition, Metabolic Dysfunction-associated Steatotic Liver disease (MASLD), emphasizes the relationship between NAFLD and cardiometabolic comorbidities. Cardiovascular disease features, such as arterial hypertension and atherosclerosis, are frequently associated with patients with MASLD. Furthermore, these patients have a high risk of developing neoplastic diseases, primarily hepatocellular carcinoma, but also extrahepatic tumors, such as esophageal, gastric, and pancreatic cancers. Moreover, several studies showed the correlation between MASLD and endocrine disease. The imbalance of the gut microbiota, systemic inflammation, obesity, and insulin resistance play a key role in the development of these complications. This narrative review aims to clarify the evolution from NAFLD to the new nomenclature MASLD and evaluate its complications.

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Global epidemiology and implications of PNPLA3 I148M variant in MASLD: a systematic review and meta-analysis

Souza,

Al-Sharif,

Diaz

et al. 2024

Journal of Clinical and Experimental Hepatology

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Usefulness of PNPLA3 variant for predicting hepatic events in steatotic liver disease: a matter of ethnicity or baseline risk?

Cited by 5 publications

References 29 publications

Global epidemiology and implications of PNPLA3 I148M variant in MASLD: a systematic review and meta-analysis

Global epidemiology and implications of PNPLA3 I148M variant in MASLD: a systematic review and meta-analysis

Dysmetabolic comorbidities and non-alcoholic fatty liver disease: a stairway to metabolic dysfunction-associated steatotic liver disease

Global epidemiology and implications of PNPLA3 I148M variant in MASLD: a systematic review and meta-analysis

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