title: The ADAMTS9 gene is associated with cognitive aging in the elderly in a Taiwanese population.
abstract: Evidence indicates that the pathophysiologic mechanisms associated with insulin resistance may contribute to cognitive aging and Alzheimer's diseases. In this study, we hypothesize that single nucleotide polymorphisms (SNPs) within insulin resistance-associated genes, such as the ADAM metallopeptidase with thrombospondin type 1 motif 9 (ADAMTS9), glucokinase regulator (GCKR), and peroxisome proliferator activated receptor gamma (PPARG) genes, may be linked with cognitive aging independently and/or through complex interactions in an older Taiwanese population. A total of 547 Taiwanese subjects aged over 60 years from the Taiwan Biobank were analyzed. Mini-Mental State Examinations (MMSE) were administered to all subjects, and MMSE scores were used to measure cognitive functions. Our data showed that four SNPs (rs73832338, rs9985304, rs4317088, and rs9831846) in the ADAMTS9 gene were significantly associated with cognitive aging among the subjects (P = 1.5 x 10-6 ~ 0.0002). This association remained significant after performing Bonferroni correction. Additionally, we found that interactions between the ADAMTS9 rs9985304 and ADAMTS9 rs76346246 SNPs influenced cognitive aging (P < 0.001). However, variants in the GCKR and PPARG genes had no association with cognitive aging in our study. Our study indicates that the ADAMTS9 gene may contribute to susceptibility to cognitive aging independently as well as through SNP-SNP interactions.
authors.affiliation: Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.|Vita Genomics, Inc., Taipei, Taiwan.|TickleFish Systems Corporation, Seattle, WA, United States of America.
authors.forename: Eugene
authors.initials: E
authors.lastname: Lin
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.|Division of Psychiatry, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Tsai
authors.affiliation: Department of Public Health, Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Po-Hsiu
authors.initials: PH
authors.lastname: Kuo
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli County, Taiwan.
authors.forename: Yu-Li
authors.initials: YL
authors.lastname: Liu
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.|Division of Psychiatry, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Albert C
authors.initials: AC
authors.lastname: Yang
authors.affiliation: Department of Agronomy, College of Agriculture & Natural Resources, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Chung-Feng
authors.initials: CF
authors.lastname: Kao
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.|Division of Psychiatry, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Cheng-Hung
authors.initials: CH
authors.lastname: Yang
mesh_terms: D000071119:ADAMTS9 Protein / Q000235:genetics*; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D000066492:Cognitive Aging / Q000502:physiology* / Q000523:psychology*; D030541:Databases, Genetic; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D047495:PPAR gamma / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D013624:Taiwan
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C485100:GCKR protein, human; D047495:PPAR gamma; D000071119:ADAMTS9 Protein