Association of interleukin-6 rs1800796 polymorphism with reduced cognitive performance in healthy older adults

Natalia Ewa Bezuch, Steven Bradburn, Sarianna Sipilä, Mati Pääsuke, Helena Gapeyeva, Andrea B. Maier, Jean Yves Hogrel, Yoann Barnouin, Gillian Butler-Browne, Marco Narici, Jamie McPhee, Chris Murgatroyd

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

With increasing life expectancy, age-associated cognitive impairment is an escalating problem worldwide. Inflammation is one of the features that characterises cognitive decline and can stimulate neurodegeneration. Interleukin 6 (IL-6) is a cytokine frequently associated with a pro-inflammatory phenotype and increased levels have been associated with the pathogenesis of dementia. The rs1800796 polymorphism in the promoter region of IL-6 gene was previously shown to influence IL-6 expression and therefore we hypothesised this gene polymorphism would be associated with IL-6 plasma levels and cognitive performance of older adults. The present study investigated the association of the rs1800796 polymorphism on plasma IL-6 levels and cognition in healthy older adults (n = 207, 74.6 ± 3.4 years, 51% female) that participated in a Pan-European project (MyoAge). The participants were assessed for working memory capacity, executive functioning, episodic memory and global cognition using the Cambridge Neuropsychological Test Automated Battery CANTAB. Fasting plasma IL-6 levels were measured by ELISA and genotyping was performed using the KASP assay. Results showed that the rs1800796 polymorphism was in Hardy-Weinberg equilibrium (P =.16) with the minor allele (C) showing a frequency of 6.3%. There were no differences in plasma IL-6 concentrations between the GG-homozygotes and C-allele carriers (P =.22). The C-allele carriers performed worse on a measure of executive functioning (P =.035) and had lower global cognitive scores (P =.045), compared to GG-homozygotes. These differences remained significant after accounting for age, sex and prior cognitive abilities (P <.05 for both). There were no differences in measures of memory (episodic and working) between the genotypes group. These findings suggest that the rs1800796 variant may be detrimental for executive functioning, but not memory, in healthy older adults.

Original languageEnglish
Pages (from-to)51-55
Number of pages5
JournalMeta Gene
Volume19
Early online date25 Oct 2018
DOIs
Publication statusPublished - Feb 2019

Fingerprint

Interleukin-6
Episodic Memory
Alleles
Homozygote
Short-Term Memory
Cognition
Aptitude
Neuropsychological Tests
Life Expectancy
Genetic Promoter Regions
Genes
Dementia
Fasting
Enzyme-Linked Immunosorbent Assay
Genotype
Cytokines
Inflammation
Phenotype

Keywords

  • Aging
  • Cognitive aging
  • IL-6
  • Inflammation
  • rs1800796

Cite this

Bezuch, Natalia Ewa ; Bradburn, Steven ; Sipilä, Sarianna ; Pääsuke, Mati ; Gapeyeva, Helena ; Maier, Andrea B. ; Hogrel, Jean Yves ; Barnouin, Yoann ; Butler-Browne, Gillian ; Narici, Marco ; McPhee, Jamie ; Murgatroyd, Chris. / Association of interleukin-6 rs1800796 polymorphism with reduced cognitive performance in healthy older adults. In: Meta Gene. 2019 ; Vol. 19. pp. 51-55.
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title = "Association of interleukin-6 rs1800796 polymorphism with reduced cognitive performance in healthy older adults",
abstract = "With increasing life expectancy, age-associated cognitive impairment is an escalating problem worldwide. Inflammation is one of the features that characterises cognitive decline and can stimulate neurodegeneration. Interleukin 6 (IL-6) is a cytokine frequently associated with a pro-inflammatory phenotype and increased levels have been associated with the pathogenesis of dementia. The rs1800796 polymorphism in the promoter region of IL-6 gene was previously shown to influence IL-6 expression and therefore we hypothesised this gene polymorphism would be associated with IL-6 plasma levels and cognitive performance of older adults. The present study investigated the association of the rs1800796 polymorphism on plasma IL-6 levels and cognition in healthy older adults (n = 207, 74.6 ± 3.4 years, 51{\%} female) that participated in a Pan-European project (MyoAge). The participants were assessed for working memory capacity, executive functioning, episodic memory and global cognition using the Cambridge Neuropsychological Test Automated Battery CANTAB. Fasting plasma IL-6 levels were measured by ELISA and genotyping was performed using the KASP assay. Results showed that the rs1800796 polymorphism was in Hardy-Weinberg equilibrium (P =.16) with the minor allele (C) showing a frequency of 6.3{\%}. There were no differences in plasma IL-6 concentrations between the GG-homozygotes and C-allele carriers (P =.22). The C-allele carriers performed worse on a measure of executive functioning (P =.035) and had lower global cognitive scores (P =.045), compared to GG-homozygotes. These differences remained significant after accounting for age, sex and prior cognitive abilities (P <.05 for both). There were no differences in measures of memory (episodic and working) between the genotypes group. These findings suggest that the rs1800796 variant may be detrimental for executive functioning, but not memory, in healthy older adults.",
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Bezuch, NE, Bradburn, S, Sipilä, S, Pääsuke, M, Gapeyeva, H, Maier, AB, Hogrel, JY, Barnouin, Y, Butler-Browne, G, Narici, M, McPhee, J & Murgatroyd, C 2019, 'Association of interleukin-6 rs1800796 polymorphism with reduced cognitive performance in healthy older adults' Meta Gene, vol. 19, pp. 51-55. https://doi.org/10.1016/j.mgene.2018.10.007

Association of interleukin-6 rs1800796 polymorphism with reduced cognitive performance in healthy older adults. / Bezuch, Natalia Ewa; Bradburn, Steven; Sipilä, Sarianna; Pääsuke, Mati; Gapeyeva, Helena; Maier, Andrea B.; Hogrel, Jean Yves; Barnouin, Yoann; Butler-Browne, Gillian; Narici, Marco; McPhee, Jamie; Murgatroyd, Chris.

In: Meta Gene, Vol. 19, 02.2019, p. 51-55.

Research output: Contribution to JournalArticleAcademicpeer-review

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AU - Bezuch, Natalia Ewa

AU - Bradburn, Steven

AU - Sipilä, Sarianna

AU - Pääsuke, Mati

AU - Gapeyeva, Helena

AU - Maier, Andrea B.

AU - Hogrel, Jean Yves

AU - Barnouin, Yoann

AU - Butler-Browne, Gillian

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AB - With increasing life expectancy, age-associated cognitive impairment is an escalating problem worldwide. Inflammation is one of the features that characterises cognitive decline and can stimulate neurodegeneration. Interleukin 6 (IL-6) is a cytokine frequently associated with a pro-inflammatory phenotype and increased levels have been associated with the pathogenesis of dementia. The rs1800796 polymorphism in the promoter region of IL-6 gene was previously shown to influence IL-6 expression and therefore we hypothesised this gene polymorphism would be associated with IL-6 plasma levels and cognitive performance of older adults. The present study investigated the association of the rs1800796 polymorphism on plasma IL-6 levels and cognition in healthy older adults (n = 207, 74.6 ± 3.4 years, 51% female) that participated in a Pan-European project (MyoAge). The participants were assessed for working memory capacity, executive functioning, episodic memory and global cognition using the Cambridge Neuropsychological Test Automated Battery CANTAB. Fasting plasma IL-6 levels were measured by ELISA and genotyping was performed using the KASP assay. Results showed that the rs1800796 polymorphism was in Hardy-Weinberg equilibrium (P =.16) with the minor allele (C) showing a frequency of 6.3%. There were no differences in plasma IL-6 concentrations between the GG-homozygotes and C-allele carriers (P =.22). The C-allele carriers performed worse on a measure of executive functioning (P =.035) and had lower global cognitive scores (P =.045), compared to GG-homozygotes. These differences remained significant after accounting for age, sex and prior cognitive abilities (P <.05 for both). There were no differences in measures of memory (episodic and working) between the genotypes group. These findings suggest that the rs1800796 variant may be detrimental for executive functioning, but not memory, in healthy older adults.

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