TNK1

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Non-receptor tyrosine-protein kinase TNK1 (EC 2.7.10.2) (CD38 negative kinase 1)

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Role of CLU, PICALM, and TNK1 Genotypes in Aging With and Without Alzheimer's Disease.

Healthy and impaired cognitive aging may be associated to different prevalences of single-nucleotide polymorphisms (SNPs). In a multicenter case-control association study, we studied the SNPs rs11136000 (clusterin, CLU), rs541458 (phosphatidylinositol binding clatrin assembly protein, PICALM), and rs1554948 (transcription factor A, and tyrosine kinase, non-receptor, 1, TNK1) according to the three age groups 50-65 years (group 1), 66-80 years (group 2), and 80 years (group 3) in 569 older subjects without cognitive impairment (NoCI) and 520 Alzheimer's disease (AD) patients. In NoCI subjects, a regression analysis suggested a relationship between age and TNK1 genotypes, with the TNK1-A/A genotype frequency that increased with higher age, and resulting in a different distribution of the TNK1-A allele. In AD patients, a regression analysis suggested a relationship between age and PICALM genotypes and TNK1 genotypes, with the PICALM-T/C and TNK1-A/A genotype frequencies that decreased with increasing age. A resulting difference in the distribution of PICALM-C allele and TNK1-A allele was also observed. The TNK1-A allele was overrepresented in NoCI subjects than in AD patients in age groups 2 and 3. These results confirmed after adjustment for apolipoprotein E polymorphism, which suggested a different role of PICALM and TNK1 in healthy and impaired cognitive aging. More studies, however, are needed to confirm the observed associations.

MeSH Terms

  • Aged
  • Aged, 80 and over
  • Aging
  • Alleles
  • Alzheimer Disease
  • Clusterin
  • Cohort Studies
  • Female
  • Fetal Proteins
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Middle Aged
  • Monomeric Clathrin Assembly Proteins
  • Polymorphism, Single Nucleotide
  • Protein-Tyrosine Kinases

Keywords

  • Alzheimer’s disease
  • Biogerontology
  • Brain aging
  • Cognition
  • Dementia
  • Genetics