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PNPLA3 is the dominant SNP linked to liver disease severity at time of first referral to a tertiary center
- Source :
- Digestive and Liver Disease. 54:84-90
- Publication Year :
- 2022
- Publisher :
- Elsevier BV, 2022.
-
Abstract
- Background Single nucleotide polymorphisms (SNPs) in genes including PNPLA3, TM6SF2, HSD17B13 and SERPINA1 have been identified as risk modifiers of progression in chronic liver disease (CLD). However, it is unclear whether genotyping for these risk variants is useful in clinical routine. Methods Liver disease severity was assessed by liver stiffness measurement (LSM) and by presence of clinical manifestations of advanced-chronic liver disease (ACLD) in 779 consecutive CLD patients at the time of referral to a tertiary center. The associations of risk variants with CLD severity were calculated individually and in a combined model using a polygenic risk-score. Results Non-alcoholic fatty liver disease (NAFLD) was the most common etiology (n = 511, 65.6%), and ACLD was present in 217 (27.9%) patients. The PNPLA3-G-allele remained independently associated with higher LSM (adjusted-B: 2.508 [95%CI: 0.887–4.130], P = 0.002) or the presence of ACLD (aOR: 1.562 [95%CI: 1.097–2.226], P = 0.013). SERPINA1-Z-allele was also independently associated with LSM (adjusted-B: 4.558 [95%CI: 1.182–7.934], P = 0.008), while the other risk alleles did not attain statistical significance. Combining these risk alleles into a polygenic risk-score was significantly associated with LSM (adjusted-B: 0.948 [95%CI: 0.153–1.743], P = 0.020). Conclusion PNPLA3 risk-variants are linked to liver disease severity at the time of first referral to an outpatient hepatology clinic.
- Subjects :
- Genetic Markers
Male
medicine.medical_specialty
Cirrhosis
17-Hydroxysteroid Dehydrogenases
Genotype
Single-nucleotide polymorphism
Disease
Chronic liver disease
Polymorphism, Single Nucleotide
Severity of Illness Index
Gastroenterology
Liver disease
Non-alcoholic Fatty Liver Disease
Risk Factors
Internal medicine
Humans
Medicine
Referral and Consultation
Alleles
Retrospective Studies
Hepatology
business.industry
Liver Diseases
Fatty liver
Membrane Proteins
Middle Aged
medicine.disease
Cross-Sectional Studies
Liver
alpha 1-Antitrypsin
Chronic Disease
Phospholipases A2, Calcium-Independent
Female
business
Acyltransferases
TM6SF2
Subjects
Details
- ISSN :
- 15908658
- Volume :
- 54
- Database :
- OpenAIRE
- Journal :
- Digestive and Liver Disease
- Accession number :
- edsair.doi.dedup.....f6a3937367fa82390b588fe82c209d3d