Evaluation of Polygenic Determinants of Non-Alcoholic Fatty Liver Disease (NAFLD) By a Candidate Genes Resequencing Strategy

Autor: Daniele Pastori, Anna Montali, Bruna De Masi, Alessia Di Costanzo, Marialuisa Sponziello, Diego Bailetti, Francesco Angelico, Laura D'Erasmo, Francesca Belardinilli, Licia Polimeni, Francesco Baratta, Giuseppe Giannini, Fabrizio Ceci, Gabriella Girelli, Antonio Angeloni, Maria Del Ben, Marcello Arca
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
Candidate gene
NASH
genetics
PNPLA3
lcsh:Medicine
Disease
0302 clinical medicine
Non-alcoholic Fatty Liver Disease
Protein Phosphatase 1
Genotype
genetics
lcsh:Science
Genetics
Multidisciplinary
Fatty liver
NASH
High-Throughput Nucleotide Sequencing
Middle Aged
Cohort
Female
030211 gastroenterology & hepatology
Lysophospholipase
Nerve Tissue Proteins
Biology
Polymorphism
Single Nucleotide
digestive system
Article
03 medical and health sciences
medicine
Humans
Genetic Predisposition to Disease
Lectins
C-Type
Gene
Alleles
Genetic Association Studies
PNPLA3
Adaptor Proteins
Signal Transducing
lcsh:R
Membrane Proteins
nutritional and metabolic diseases
Lipase
medicine.disease
Genetic architecture
digestive system diseases
030104 developmental biology
Chondroitin Sulfate Proteoglycans
lcsh:Q
Neurocan
TM6SF2
Zdroj: Scientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
Scientific Reports
ISSN: 2045-2322
Popis: NAFLD is a polygenic condition but the individual and cumulative contribution of identified genes remains to be established. To get additional insight into the genetic architecture of NAFLD, GWAS-identified GCKR, PPP1R3B, NCAN, LYPLAL1 and TM6SF2 genes were resequenced by next generation sequencing in a cohort of 218 NAFLD subjects and 227 controls, where PNPLA3 rs738409 and MBOAT7 rs641738 genotypes were also obtained. A total of 168 sequence variants were detected and 47 were annotated as functional. When all functional variants within each gene were considered, only those in TM6SF2 accumulate in NAFLD subjects compared to controls (P = 0.04). Among individual variants, rs1260326 in GCKR and rs641738 in MBOAT7 (recessive), rs58542926 in TM6SF2 and rs738409 in PNPLA3 (dominant) emerged as associated to NAFLD, with PNPLA3 rs738409 being the strongest predictor (OR 3.12, 95% CI, 1.8-5.5, P 0.28 was associated with a 3-fold increased risk of NAFLD. Interestingly, rs61756425 in PPP1R3B and rs641738 in MBOAT7 genes were predictors of NAFLD severity. Overall, TM6SF2, GCKR, PNPLA3 and MBOAT7 were confirmed to be associated with NAFLD and a score based on these genes was highly predictive of this condition. In addition, PPP1R3B and MBOAT7 might influence NAFLD severity.
Databáze: OpenAIRE
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