Polymorphisms in cytokine genes influence cognitive and functional performance in a population aged 75 years and above

Int J Geriatr Psychiatry. 2017 Dec;32(12):1401-1410. doi: 10.1002/gps.4627. Epub 2016 Nov 28.

Abstract

Objective: To investigate the frequency of the cytokine single nucleotide polymorphisms (SNPs) tumor necrosis factor (TNF)-α -308G > A, tumor growth factor (TGF)-β1 codon +10C > T, TGF-β1 codon +25G > C, interleukin (IL)-10 -1082A > G, IL-10 -819C > T, IL-10 -592C > A, IL-6 -174G > C, and IFN-γ +874T > A in a sample of healthy and cognitively impaired elderlies and to verify the probable association between these SNPs and cognitive and functional performance of subjects aged 75 years and above.

Methods: 259 Brazilian subjects were included, comprising 81 with cognitive impairment no dementia (CIND) and 54 demented seniors (together made up the cognitively impaired group, CI) and 124 age-matched and gender-matched cognitively healthy controls (CHS). The genotyping was performed by multiplex polymerase chain reaction. The cognitive performance was evaluated by Mini-Mental State Examination Brief Cognitive Screening Battery. The functional performance was accessed by Functional Activities Questionnaire.

Results: The CClower genotype of TGF-β1 codon +25G > C was frequent in both patient groups. The TThigher genotype of INF-γ +874T > A was less frequent in the dementia group. IL-10 haplotypes of lower expression were more frequent among CIND and demented patients. In CI, individuals with genetic variants that produce higher expression of TGF-β1, INF-γ, and IL-10 showed better normalized cognitive performance. Additionally, the Alower allele of INF-γ +874T > A was related to worse functional performance in CI, while the Alower allele of TNF-α -308G > A was associated with better cognitive and functional scores in the CIND group.

Conclusions: Our findings suggest a potential role for certain cytokine SNPs in the development of CIND and dementia, which may influence the functional and cognitive performance of these patients. Copyright © 2016 John Wiley & Sons, Ltd.

Keywords: cognition; cytokines; dementia; functionality; inflammation; polymorphisms.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alleles
  • Brazil
  • Case-Control Studies
  • Cognitive Dysfunction / genetics*
  • Cytokines / genetics*
  • Female
  • Genotype
  • Humans
  • Interferon-gamma / genetics
  • Interleukin-10 / genetics
  • Interleukin-6 / genetics
  • Male
  • Polymorphism, Single Nucleotide*
  • Transforming Growth Factor beta1 / genetics
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Cytokines
  • IL10 protein, human
  • Interleukin-6
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interferon-gamma