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Genome-wide scan revealed that polymorphisms in the PNPLA3, SAMM50, and PARVB genes are associated with development and progression of nonalcoholic fatty liver disease in Japan
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Genome-wide scan revealed that polymorphisms in the PNPLA3, SAMM50, and PARVB genes are associated with development and progression of nonalcoholic fatty liver disease in Japan
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Genome-wide scan revealed that polymorphisms in the PNPLA3, SAMM50, and PARVB genes are associated with development and progression of nonalcoholic fatty liver disease in Japan
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Journal Article
Genome-wide scan revealed that polymorphisms in the PNPLA3, SAMM50, and PARVB genes are associated with development and progression of nonalcoholic fatty liver disease in Japan
2013
Overview
We examined the genetic background of nonalcoholic fatty liver disease (NAFLD) in the Japanese population, by performing a genome-wide association study (GWAS). For GWAS, 392 Japanese NAFLD subjects and 934 control individuals were analyzed. For replication studies, 172 NAFLD and 1,012 control subjects were monitored. After quality control, 261,540 single-nucleotide polymorphisms (SNPs) in autosomal chromosomes were analyzed using a trend test. Association analysis was also performed using multiple logistic regression analysis using genotypes, age, gender and body mass index (BMI) as independent variables. Multiple linear regression analyses were performed to evaluate allelic effect of significant SNPs on biochemical traits and histological parameters adjusted by age, gender, and BMI. Rs738409 in the
PNPLA3
gene was most strongly associated with NAFLD after adjustment (
P
= 6.8 × 10
−14
, OR = 2.05). Rs2896019, and rs381062 in the
PNPLA3
gene, rs738491, rs3761472, and rs2143571 in the
SAMM50
gene, rs6006473, rs5764455, and rs6006611 in the
PARVB
gene had also significant
P
values (<2.0 × 10
−10
) and high odds ratios (1.84–2.02). These SNPs were found to be in the same linkage disequilibrium block and were associated with decreased serum triglycerides and increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in NAFLD patients. These SNPs were associated with steatosis grade and NAFLD activity score (NAS). Rs738409, rs2896019, rs738491, rs6006473, rs5764455, and rs6006611 were associated with fibrosis. Polymorphisms in the
SAMM50
and
PARVB
genes in addition to those in the
PNPLA3
gene were observed to be associated with the development and progression of NAFLD.
Publisher
Springer-Verlag,Springer,Springer Nature B.V
Subject
/ Adult
/ Age
/ Aged
/ Alanine Transaminase - blood
/ Alanine Transaminase - genetics
/ Asian Continental Ancestry Group
/ Aspartate Aminotransferases - blood
/ Aspartate Aminotransferases - genetics
/ Biomedical and Life Sciences
/ Biopsy
/ Female
/ Fibrosis
/ Genes
/ Genome-Wide Association Study
/ Genomes
/ Genomics
/ Genotype
/ Humans
/ Japan
/ Male
/ Medicine
/ Membrane Proteins - genetics
/ Membrane Proteins - metabolism
/ Mitochondrial Proteins - genetics
/ Mitochondrial Proteins - metabolism
/ Non-alcoholic Fatty Liver Disease
/ Polymorphism, Single Nucleotide
/ Science
