title: MAPKAP1 rs10118570 polymorphism is associated with anti-infection and anti-hepatic fibrogenesis in schistosomiasis japonica.
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.
authors.affiliation: Guangdong Province Key Laboratory of Medical Molecular Diagnosis, Department of Clinical Oncology, Guangdong Medical College, Zhanjiang/Dongguan, China; Peking University Shenzhen Hospital, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center, Shenzhen, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
authors.forename: Jinfang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China.
authors.forename: Wenguo
authors.initials: W
authors.lastname: Fan
authors.affiliation: School of Biomedical Informatics, University of Texas, Houston, Texas, United States of America.
authors.forename: Yunguo
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Clinical Imaging Research Center, A*STAR-NUS, Singapore, Singapore.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yan
authors.affiliation: School of Life Sciences, Hunan University of Science and Technology, Xiangtan, China.
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: Center for Clinical and Translational Science, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Lang
authors.initials: L
authors.lastname: Wu
authors.affiliation: Guangdong Province Key Laboratory of Medical Molecular Diagnosis, Department of Clinical Oncology, Guangdong Medical College, Zhanjiang/Dongguan, China.
authors.forename: Hongjing
authors.initials: H
authors.lastname: Cui
authors.affiliation: Guangdong Province Key Laboratory of Medical Molecular Diagnosis, Department of Clinical Oncology, Guangdong Medical College, Zhanjiang/Dongguan, China.
authors.forename: Haiqing
authors.initials: H
authors.lastname: Luo
authors.affiliation: Immunity and Biochemical Research Lab, Zhejiang Academy of Medical Sciences, Hangzhou, China.
authors.forename: Qingming
authors.initials: Q
authors.lastname: Kong
authors.affiliation: Schistosomiasis Institute, Hubei Academy of Preventive Medicine, Hubei Provincial Center for Disease Control and Prevention, Wuhan, China.
authors.forename: Li
authors.initials: L
authors.lastname: Tang
authors.affiliation: Department of Human Anatomy, Guangzhou Medical University, Guangzhou, China.
authors.forename: Shuilong
authors.initials: S
authors.lastname: Leng
authors.affiliation: Department of Laboratory Medicine, Ningbo No.2 Hospital, Ningbo, China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China; Guangzhou Institute of Advanced Technology, Chinese Academy of Sciences, Guangzhou, China.
authors.forename: Weiming
authors.initials: W
authors.lastname: Fu
authors.affiliation: Peking University Shenzhen Hospital, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center, Shenzhen, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Xiao
authors.affiliation: Guangdong Province Key Laboratory of Medical Molecular Diagnosis, Department of Clinical Oncology, Guangdong Medical College, Zhanjiang/Dongguan, China; Institute of Molecular Medicine and Genetics, Department of Neuroscience and Regenerative Medicine, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Dongpei
authors.initials: D
authors.lastname: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D058069:Neglected Diseases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012554:Schistosomiasis japonica / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C493277:MAPKAP1 protein, human