Associations of cytokine genes with Alzheimer's disease and depression in an elderly Korean population.

Abstract

BACKGROUND:

Inflammatory processes regulated by cytokines are important in the aetiology of Alzheimer's disease (AD) and depression. Differences in transcriptional activities associated with several genetic polymorphisms affect cytokine production. We investigated the involvement of alleles associated with higher production of proinflammatory and lower production of anti-inflammatory cytokines in AD and depression in a community-dwelling sample of elderly individuals.

METHOD:

A total of 732 community-dwelling elders were clinically evaluated for AD applying the NINCDS-ADRDA criteria and for depression applying the Geriatric Mental State Schedule. Genotyping was performed for six proinflammatory (interleukin (IL)-1β -511C/T and +3953C/T, IL-6 -174G/C, IL-8 -251T/A, tumour necrosis factor (TNF)-α -850C/T) and two anti-inflammatory (IL-4 +33T/C, IL-10 -1082G/A) cytokines. The sums of risk alleles of proinflammatory and anti-inflammatory cytokine genes were estimated. Age, gender, education and apolipoprotein E genotype were considered covariates.

RESULTS:

TNF-α -308G/A and IL-8 -251T/A were significantly associated with AD and IL-1β +3953C/T with late-life depression, while the significance of these associations was lost after Bonferroni correction. A greater number of risk alleles producing proinflammatory cytokines was significantly associated with AD, but not with depression, after adjustment for the covariates. No association was found between an increased number of risk alleles for anti-inflammatory cytokine production and either AD or depression.

CONCLUSIONS:

The present findings support the inflammatory hypothesis in the aetiology of AD as measured by several cytokine genes associated with increased proinflammatory cytokine production.

• Authors: Hee-Ju Kang, Jae-Min Kim, Sung-Wan Kim, Il-Seon Shin, Sung-Woo Park, Young-Hoon Kim, Jin-Sang Yoon
• Journal: Journal of neurology, neurosurgery, and psychiatry (J Neurol Neurosurg Psychiatry) Vol. 86 Issue 9 Pg. 1002-7 (Sep 2015) ISSN: 1468-330X [Electronic] England
• PMID: 25315113 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Chemical References

• Cytokines
• Interleukin-1beta
• Interleukin-8
• Tumor Necrosis Factor-alpha

Topics

• Aged
• Aged, 80 and over
• Alzheimer Disease (genetics)
• Asian People (genetics)
• Cytokines (genetics)
• Depression (genetics)
• Depressive Disorder (genetics)
• Female
• Genetic Association Studies
• Genetic Predisposition to Disease
• Genotype
• Humans
• Interleukin-1beta (genetics)
• Interleukin-8 (genetics)
• Male
• Polymorphism, Single Nucleotide
• Republic of Korea
• Tumor Necrosis Factor-alpha (genetics)