Age, BMI, and Type 2 Diabetes Modify the Relationship Between PNPLA3 and Advanced Fibrosis in Children and Adults With NAFLD.
Clin Gastroenterol Hepatol
; 22(5): 1024-1036.e2, 2024 May.
Article
in En
| MEDLINE
| ID: mdl-38145725
ABSTRACT
BACKGROUND & AIMS:
PNPLA3 G-allele is an important determinant of disease severity in nonalcoholic fatty liver disease (NAFLD). Here, we investigated the effect of age, body mass index (BMI), and type 2 diabetes mellitus (T2DM) on the relationship between PNPLA3 G-allele and advanced fibrosis in adults and children with histologically characterized NAFLD.METHODS:
A total of 1047 children and 2057 adults were included. DNA was genotyped for rs738409 in duplicate. Primary outcome of interest was advanced fibrosis (fibrosis stage ≥3). Regression analyses were performed after controlling for relevant covariates. An additive model was used to assess the effect of PNPLA3 G-allele (CC vs CG vs GG).RESULTS:
PNPLA3 G-allele was significantly associated with advanced fibrosis in children (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.16-2.09) and adults (OR, 1.55; 95% CI, 1.16-1.54). Across the cohort, older age significantly increased the risk for advanced fibrosis for PNPLA3 CC (OR, 1.019; 95% CI, 1.013-1.026), CG (OR, 1.024; 95% CI, 1.018-1.030), and GG (OR, 1.03; 95% CI, 1.023-1.037) genotypes. BMI significantly increased the relationship between PNPLA3 genotypes and advanced fibrosis in children and adults. A BMI of 30 kg/m2 was the cutoff beyond which PNPLA3 G-allele had exponential effect on the risk for advanced fibrosis in children and adults. T2DM significantly worsened the relationship between PNPLA3 G-allele and advanced fibrosis in children and adults (interaction P < .01 for both).CONCLUSIONS:
Age, BMI, and T2DM modify the risk of advanced fibrosis associated with PNPLA3 G-allele. Preventing or reversing T2DM and obesity in persons carrying PNPLA3 G-allele may lower the risk for advanced fibrosis in NAFLD.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Acyltransferases
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Body Mass Index
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Diabetes Mellitus, Type 2
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Phospholipases A2, Calcium-Independent
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Non-alcoholic Fatty Liver Disease
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Lipase
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Liver Cirrhosis
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Membrane Proteins
Limits:
Adolescent
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Adult
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Aged
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Child
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Female
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Humans
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Male
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Middle aged
Language:
En
Journal:
Clin Gastroenterol Hepatol
Journal subject:
GASTROENTEROLOGIA
Year:
2024
Document type:
Article
Country of publication:
Estados Unidos