title: Susceptible gene of stasis-stagnation constitution from genome-wide association study related to cardiovascular disturbance and possible regulated traditional Chinese medicine.
abstract: BACKGROUND
  This study identified susceptible loci related to the Yu-Zhi (YZ) constitution, which indicates stasis-stagnation, found in a genome-wide association study (GWAS) in patients with type 2 diabetes and possible regulated traditional Chinese medicine (TCM) using docking and molecular dynamics (MD) simulation.
  
  
  METHODS
  Non-aboriginal Taiwanese with type 2 diabetes were recruited. Components of the YZ constitution were assessed by a self-reported questionnaire. Genome-wide SNP genotypes were obtained using the Illumina HumanHap550 platform. The world's largest TCM database ( http://tcm.cmu.edu.tw/ ) was employed to investigate potential compounds for PON2 interactions.
  
  
  RESULTS
  The study involved 1,021 unrelated individuals with type 2 diabetes. Genotyping data were obtained from 947 of the 1,021 participants. The GWAS identified 22 susceptible single nucleotide polymorphisms on 13 regions of 11 chromosomes for the YZ constitution. Genotypic distribution showed that PON2 on chromosome 7 was most significantly associated with the risk of the YZ constitution. Docking and MD simulation indicated 13-hydroxy-(9E_11E)-octadecadienoic acid was the most stable TCM ligand.
  
  
  CONCLUSIONS
  Risk loci occurred in PON2, which has antioxidant properties that might protect against atherosclerosis and hyperglycemia, showing it is a susceptible gene for the YZ constitution and possible regulation by 13-hydroxy-(9E_11E)-octadecadienoic acid.
authors.affiliation: Graduate Institute of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan. huangimd@gmail.com.|Department of Integration of Traditional Chinese and Western Medicine, China Medical University Hospital, Taichung, 40447, Taiwan. huangimd@gmail.com.|School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan. huangimd@gmail.com.
authors.forename: Kuo-Chin
authors.initials: KC
authors.lastname: Huang
authors.affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, Taichung, 40402, Taiwan. helix70258@gmail.com.
authors.forename: Hung-Jin
authors.initials: HJ
authors.lastname: Huang
authors.affiliation: School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan. chingchu@ms15.hinet.net.|Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taichung, 40447, Taiwan. chingchu@ms15.hinet.net.
authors.forename: Ching-Chu
authors.initials: CC
authors.lastname: Chen
authors.affiliation: School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan. chingchu@ms15.hinet.net.|Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taichung, 40447, Taiwan. chingchu@ms15.hinet.net.
authors.forename: Chwen-Tzuei
authors.initials: CT
authors.lastname: Chang
authors.affiliation: School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan. yuan.w16@msa.hinet.net.|Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taichung, 40447, Taiwan. yuan.w16@msa.hinet.net.
authors.forename: Tzu-Yuan
authors.initials: TY
authors.lastname: Wang
authors.affiliation: School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan. paishulan@yahoo.com.tw.|Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taichung, 40447, Taiwan. paishulan@yahoo.com.tw.
authors.forename: Rong-Hsing
authors.initials: RH
authors.lastname: Chen
authors.affiliation: Human Genetic Center, Department of Medical Research, China Medical University Hospital, 40402, Taichung, Taiwan. ycc929@MIT.EDU.|Research Center for Chinese Medicine & Acupuncture, China Medical University, Taichung, 40402, Taiwan. ycc929@MIT.EDU.|Department of Biotechnology, Asia University, Taichung, 41354, Taiwan. ycc929@MIT.EDU.
authors.forename: Yu-Chian
authors.initials: YC
authors.lastname: Chen
authors.affiliation: School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan. d0704@mail.cmuh.org.tw.|Human Genetic Center, Department of Medical Research, China Medical University Hospital, 40402, Taichung, Taiwan. d0704@mail.cmuh.org.tw.|Department of Medical Genetics, Medical Research and Pediatrics, China Medical University Hospital, No. 2, Yuh Der Road, Taichung, Taiwan. d0704@mail.cmuh.org.tw.
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
mesh_terms: D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008516:Medicine, Chinese Traditional; D008875:Middle Aged; D056004:Molecular Dynamics Simulation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*