The ADAMTS9 gene is associated with cognitive aging in the elderly in a Taiwanese population

PLoS One. 2017 Feb 22;12(2):e0172440. doi: 10.1371/journal.pone.0172440. eCollection 2017.

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.

MeSH terms

  • ADAMTS9 Protein / genetics*
  • Adaptor Proteins, Signal Transducing / genetics
  • Aged
  • Aged, 80 and over
  • Cognitive Aging / physiology*
  • Cognitive Aging / psychology*
  • Databases, Genetic
  • Female
  • Genetic Association Studies
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • PPAR gamma / genetics
  • Polymorphism, Single Nucleotide*
  • Taiwan

Substances

  • Adaptor Proteins, Signal Transducing
  • GCKR protein, human
  • PPAR gamma
  • ADAMTS9 Protein

Grants and funding

This work was supported by the Ministry of Economic Affairs in Taiwan (http://www.moea.gov.tw/; SBIR Grant S099000280249-154; EL), by Taipei Veterans General Hospital, Taiwan (www.vghtpe.gov.tw/; Grants VGHUST103-G1-4-1, V105C-008, and V105E17-002-MY2-1; SJT), by the National Health Research Institutes, Taiwan (Grant NP-105-SP-04; YLL), and by the Ministry of Science and Technology, Taiwan (https://www.most.gov.tw/; Grant MST 102-2314-B-002-117-MY3; PHK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The commercial affiliation, Vita Genomics, Inc., provided support in the form of salary for author EL, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the ‘author contributions’ section.