Genome-wide scan revealed that polymorphisms in the PNPLA3, SAMM50, and PARVB genes are associated with development and progression of nonalcoholic ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2013-07

AUTHORS

Takuya Kitamoto, Aya Kitamoto, Masato Yoneda, Hideyuki Hyogo, Hidenori Ochi, Takahiro Nakamura, Hajime Teranishi, Seiho Mizusawa, Takato Ueno, Kazuaki Chayama, Atsushi Nakajima, Kazuwa Nakao, Akihiro Sekine, Kikuko Hotta

ABSTRACT

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. More... »

PAGES

783-792

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00439-013-1294-3

DOI

http://dx.doi.org/10.1007/s00439-013-1294-3

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1012648801

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/23535911


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