MAPKAP1 rs10118570 polymorphism is associated with anti-infection and anti-hepatic fibrogenesis in schistosomiasis japonica

PLoS One. 2014 Aug 25;9(8):e105995. doi: 10.1371/journal.pone.0105995. eCollection 2014.

Abstract

Chronic infection with Schistosoma japonicum is an important cause of hepatic fibrosis (HF). Human 9q33.3 is one of the most important loci for stress-related diseases. We examined the potential associations of 43 single-nucleotide polymorphisms (SNPs) with S. japonicum infection and HF in epidemic region in China. We identified a SNP (rs10118570 GG in mitogen-activated protein kinase associated protein 1, MAPKAP1) contributes to anti-infection (adjusted OR = 0.35) and anti-fibrogenesis (adjusted RR = 0.44) in the discovery study. Replicative and combined studies showed consistent protective quality for this genotype (replicative: adjusted OR = 0.37 for anti-infection, and adjusted RR = 0.40 for anti-fibrogenesis; Combined: adjusted OR = 0.45 for anti-infection, and adjusted RR = 0.42 for anti-fibrogenesis). Univariate and multivariate analysis in the discovery, replicative and combined studies, suggested that durations (years), splenomegaly, serum ALB and rs10118570 were independent predictors influencing the fibrogenesis. The analysis of gene-gene interaction showed rs10118570 functions independently. We conclude that MAPKAP1 may represent a novel anti-infection and anti-fibrogenesis genomic locus in chronic schistosomiasis japonica. And rs10118570 may be a potential biomarker and target for the treatment of this life-threatening ancient disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adult
  • Case-Control Studies
  • Female
  • Genetic Association Studies / methods
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Liver Cirrhosis / genetics
  • Male
  • Middle Aged
  • Neglected Diseases / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Schistosomiasis japonica / genetics*

Substances

  • Adaptor Proteins, Signal Transducing
  • MAPKAP1 protein, human

Grants and funding

This work was supported by National Natural Science Foundation of China Grants 81071697, 31100914, 30700436, 81271166 and 81201831; Natural Science Foundation of Guangdong Province Grant S2011040003694; Research Project of Science and Information Technology of Guangzhou City Grant 2012J4100075, 12C22061657; Research Project of Initial for Talent Research in Guangdong Medical College XB1382, GZ1131-B. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.