Combining Genetic Variants to Improve Risk Prediction for NAFLD and Its Progression to Cirrhosis: A Proof of Concept Study.
Can J Gastroenterol Hepatol
; 2018: 7564835, 2018.
Article
em En
| MEDLINE
| ID: mdl-29732362
ABSTRACT
Background & Aims:
Identifying NAFLD patients at risk of progression is crucial to orient medical care and resources. We aimed to verify if the effects determined by different single nucleotide polymorphisms (SNPs) could add up to multiply the risk of NAFLD and NASH-cirrhosis.Methods:
Three study populations, that is, patients diagnosed with NASH-cirrhosis or with noncirrhotic NAFLD and healthy controls, were enrolled. PNPLA3 rs738409, TM6SF2 rs58542926, KLF6 rs3750861, SOD2 rs4880, and LPIN1 rs13412852 were genotyped.Results:
One hundred and seven NASH-cirrhotics, 93 noncirrhotic NAFLD, and 90 controls were enrolled. At least one difference in allele frequency between groups was significant, or nearly significant, for the PNPLA3, TM6SF2, and KLF6 variants (p < 0.001, p < 0.05, and p = 0.06, resp.), and a risk score based on these SNPs was generated. No differences were observed for SOD2 and LPIN1 SNPs. When compared to a score of 0, a score of 1-2 quadrupled, and a score of 3-4 increased 20-fold the risk of noncirrhotic NAFLD; a score of 3-4 quadrupled the risk of NASH-cirrhosis.Conclusions:
The effects determined by disease-associated variants at different loci can add up to multiply the risk of NAFLD and NASH-cirrhosis. Combining different disease-associated variants may represent the way for genetics to keep strength in NAFLD diagnostics.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Superóxido Dismutase
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Fosfatidato Fosfatase
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Hepatopatia Gordurosa não Alcoólica
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Fator 6 Semelhante a Kruppel
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Lipase
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Cirrose Hepática
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Proteínas de Membrana
Tipo de estudo:
Etiology_studies
/
Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
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Aged
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Humans
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Middle aged
Idioma:
En
Revista:
Can J Gastroenterol Hepatol
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Itália