Impact of PNPLA3 rs738409 Polymorphism on the Development of Liver-Related Events in Patients With Nonalcoholic Fatty Liver Disease.
Clin Gastroenterol Hepatol
; 21(13): 3314-3321.e3, 2023 12.
Article
en En
| MEDLINE
| ID: mdl-37149016
ABSTRACT
BACKGROUND AND AIMS:
Nonalcoholic fatty liver disease (NAFLD) is a complex disease, resulting from the interplay between environmental determinants and genetic variations. Single nucleotide polymorphism rs738409 C>G in the PNPLA3 gene is associated with hepatic fibrosis and with higher risk of developing hepatocellular carcinoma. Here, we analyzed a longitudinal cohort of biopsy-proven NAFLD subjects with the aim to identify individuals in whom genetics may have a stronger impact on disease progression.METHODS:
We retrospectively analyzed 756 consecutive, prospectively enrolled biopsy-proven NAFLD subjects from Italy, United Kingdom, and Spain who were followed for a median of 84 months (interquartile range, 65-109 months). We stratified the study cohort according to sex, body mass index (BMI) ≥30 kg/m2) and age (≥50 years). Liver-related events (hepatic decompensation, hepatic encephalopathy, esophageal variceal bleeding, and hepatocellular carcinoma) were recorded during the follow-up and the log-rank test was used to compare groups.RESULTS:
Overall, the median age was 48 years and most individuals were men (64.7%). The PNPLA3 rs738409 genotype was CC in 235 (31.1%), CG in 328 (43.4%), and GG in 193 (25.5%) patients. At univariate analysis, the PNPLA3 GG risk genotype was associated with female sex and inversely related to BMI (odds ratio, 1.6; 95% confidence interval, 1.1-2.2; P = .006; and odds ratio, 0.97; 95% confidence interval, 0.94-0.99; P = .043, respectively). Specifically, PNPLA3 GG risk homozygosis was more prevalent in female vs male individuals (31.5% vs 22.3%; P = .006) and in nonobese compared with obese NAFLD subjects (50.0% vs 44.2%; P = .011). Following stratification for age, sex, and BMI, we observed an increased incidence of liver-related events in the subgroup of nonobese women older than 50 years of age carrying the PNPLA3 GG risk genotype (log-rank test, P = .0047).CONCLUSIONS:
Nonobese female patients with NAFLD 50 years of age and older, and carrying the PNPLA3 GG risk genotype, are at higher risk of developing liver-related events compared with those with the wild-type allele (CC/CG). This finding may have implications in clinical practice for risk stratification and personalized medicine.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Várices Esofágicas y Gástricas
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Carcinoma Hepatocelular
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Enfermedad del Hígado Graso no Alcohólico
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Neoplasias Hepáticas
Tipo de estudio:
Prognostic_studies
Límite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Clin Gastroenterol Hepatol
Asunto de la revista:
GASTROENTEROLOGIA
Año:
2023
Tipo del documento:
Article
País de afiliación:
Italia