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Commonly studied polymorphisms in inflammatory cytokine genes show only minor effects on mortality and related risk factors in nonagenarians.

ABSTRACT: Systemic low-grade inflammation is consistently associated with functional status, cognitive functioning, multimorbidity, and survival in oldest olds. If inflammation is either a cause or a consequence of age-related pathology, genetic determinants of late-life survival can reside in cytokine genes polymorphisms, regulating inflammatory responses. The aim of this study was to test associations between commonly studied polymorphisms in interleukin (IL)6, IL10, IL15, and IL18, and tumor necrosis factor-alpha genes and late-life survival in a longitudinal cohort of nonagenarians: the Danish 1905 cohort. Additionally, associations were investigated between inflammatory markers and major predictors of mortality as cognitive and functional status. Modest sex-specific associations were found with survival, cognitive functioning, and handgrip strength. Evaluation of combined genotypes indicated that, in nonagenarian men, the balance of pro- and anti-inflammatory activity at IL18 and IL10 loci is protective against cognitive decline. In conclusion, in this large study with virtually complete follow-up, commonly studied polymorphisms in cytokine genes do not have a major impact on late-life survival or associated risk phenotypes.

SUBMITTER: Dato S

PROVIDER: S-EPMC2822285 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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Commonly studied polymorphisms in inflammatory cytokine genes show only minor effects on mortality and related risk factors in nonagenarians.

Dato Serena S Krabbe Karen S KS Thinggaard Mikael M Pedersen Bente K BK Christensen Kaare K Bruunsgaard Helle H Christiansen Lene L

The journals of gerontology. Series A, Biological sciences and medical sciences 20100118 3

Systemic low-grade inflammation is consistently associated with functional status, cognitive functioning, multimorbidity, and survival in oldest olds. If inflammation is either a cause or a consequence of age-related pathology, genetic determinants of late-life survival can reside in cytokine genes polymorphisms, regulating inflammatory responses. The aim of this study was to test associations between commonly studied polymorphisms in interleukin (IL)6, IL10, IL15, and IL18, and tumor necrosis f ...[more]

PMID: 20083555

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Project description:Introduction: Studies on the association between gene polymorphisms of various inflammatory factors and liver cirrhosis have been inconsistent. The purpose of this study was to comprehensively summarize the available evidence on the association between gene polymorphisms of inflammatory factors and liver cirrhosis through a systematic review. Methods: We searched databases of PubMed, EMBASE, Web of Science, and the Cochrane Library for relevant articles published from building databases to 25 September 2022. A systematic review and meta-analysis were performed to investigate the association between gene polymorphisms of various inflammatory factors and liver cirrhosis. Odds ratios (OR) and 95% confidence intervals (CI) were used to assess the strength of association. Results: A total of 43 articles were included in the systematic review and of them, 22 articles were included in the meta-analysis. The gene polymorphisms of IL-10-1082 GA + AA vs. GG (OR = 1.43, 95% CI = 1.12-1.83), IL-10-1082 AA vs. GG (OR = 2.03, 95% CI = 1.36-3.02), IL-18 -137 GG vs. CC (OR = 3.84, 95% CI = 1.29-11.40), TGF-β1 -509 T vs. C (OR = 2.52, 95% CI = 1.42-4.48), and IFN-γ +874 T vs. A (OR = 1.98, 95% CI = 1.32-2.98) were associated with liver cirrhosis significantly and no association was observed in other gene polymorphisms included in the meta-analysis. The review of inflammatory factors gene polymorphisms that were only reported by a single study indicated 19 gene polymorphisms were risk factors and 4 gene polymorphisms were protective factors for liver cirrhosis, while the association between other 27 gene polymorphisms and liver cirrhosis were not statistically significant. Discussion: This study suggests that IL-10 -1082G/A, IL-18 -137G/C, TGF-β1 -509T/C, and IFN-γ +874T/A were potentially associated with the risk of liver cirrhosis susceptibility. These findings may provide comprehensive evidence for genetic susceptibility and immunogenetic pathology of liver cirrhosis.

Dataset Information

Commonly studied polymorphisms in inflammatory cytokine genes show only minor effects on mortality and related risk factors in nonagenarians.

Publications

Commonly studied polymorphisms in inflammatory cytokine genes show only minor effects on mortality and related risk factors in nonagenarians.

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