Regulation of Human Life Histories

Bodegom, David van; May, Linda; Meij, Hans J.; Westendorp, Rudi G. J.

doi:10.1196/annals.1395.007

Cited by 43 publications

(32 citation statements)

References 80 publications

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“…An acute inflammatory response is beneficial for survival, but a chronic inflammatory state accompanies (and contributes to) age-associated diseases such as neurodegenerative disorders, autoimmunity and cancer Van Bodegom et al 2007). A reliable marker of inflammation is interleukin-6 (IL-6), the circulating level of which is increased in chronic diseases and aging (Mastorakos and Ilias 2006;Jylhä et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Interleukin-6 plasma level increases with age in an Italian elderly population (“The Treviso Longeva”–Trelong–study) with a sex-specific contribution of rs1800795 polymorphism

Albani

Batelli

Polito

et al. 2009

AGE

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The transcription rate of interleukin-6 (IL-6) can be reduced by the C-allele of a polymorphism (rs1800795) located in the 5′-flanking region of the IL-6 gene (NM_000600), and IL-6 plasma levels increase with age. We assembled an elderly Italian population ["The Treviso Longeva (Trelong) study", age range 70-106 years, n = 668 subjects] and assessed rs1800795 genotype and plasma IL-6 concentrations. The rs1800795 genotype was also assessed in an independent Italian study ("Milan" study, age range 70-96, n= 245 subjects). To verify an age-or sex-specific effect of rs1800795 genotype we compared people younger (70-85) and older (85+) than 85 years of age. We found a significant reduction in the frequency of rs1800795 C/C genotype in 85+ men from the Trelong study, while in the Milan study this data did not reach significance. However, considering the two studies together, the frequency of the rs1800795 C/C genotype was significantly lower in 85+ than in 70-85 males (4.0% and 10.7%, respectively), while it remained unchanged in females. As for IL-6 plasma levels, after a multivariate analysis to control for confounders, a correlation between age and plasma IL-6 concentrations was revealed (P <0.0001). An increase in circulating IL-6 levels in the entire 85+ group compared to the 70-85 group (P<0.05, Tukey′s test) was also noticed. We suggest a sex-specific pattern for genetic variability linked to inflammatory response and longevity, consistent with the age-related increase in IL-6.

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Section: Introductionmentioning

confidence: 99%

Interleukin-6 plasma level increases with age in an Italian elderly population (“The Treviso Longeva”–Trelong–study) with a sex-specific contribution of rs1800795 polymorphism

Albani

Batelli

Polito

et al. 2009

AGE

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“…[1][2][3] The innate cytokine response is a crucial component in the host response to pathogens and has been shown to be under tight genetic control. [4][5][6] However, essentially all studies on the relationship between genetic variation and cytokine production have been performed in populations living in environments with a low exposure to pathogens, and little is known about the role of genetics on cytokine production capacity in adverse environments.…”

Section: Introductionmentioning

confidence: 99%

The influence of genetic variation on innate immune activation in an environment with high infectious pressure

et al. 2011

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Interleukin-10 (IL-10) production is under tight genetic control in populations living in affluent environments. However, little is known about the role of IL10 genetics on cytokine production in populations living in environments with high infectious pressure. We have previously reported that, in a rural Ghanaian population, the most common IL10 haplotype associates with a pro-inflammatory response. Here, we aim to replicate these findings in an independent sample of the same population 2 years later. IL-10 and tumour necrosis factor-a (TNF-a) protein concentrations were determined in whole-blood samples ex vivo stimulated with lipopolysaccharide and zymosan in 2006 (n ¼ 615) and 2008 (n ¼ 647). The association between IL10 single nucleotide polymorphisms and Z-scores of IL-10 and TNF-a levels was analysed in each population subset. The most common IL10 haplotype was associated with a significantly lower IL-10 production and nonsignificantly increased TNF-a levels. The correlation between repeated cytokine assays, based on 111 individuals with measurements in both 2006 and 2008, was r ¼ 0.53 (Po0.001) for IL-10 and r ¼ 0.36 (Po0.001) for TNF-a. The replication of our previously found effect of variation in the IL10 gene on IL-10 production and the correlation between repeated cytokine stimulation assays provide evidence that IL10 genetics have an important role in regulating the host response under high infectious pressure.

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“…There is vast literature indicating that proinflammatory immune responses might have beneficial consequences for survival, but might be detrimental for reproduction. 34 Therefore, we expect that, with regard to TLR polymorphisms as well, selection will be balanced. Knowing cause-specific mortality in the study population would provide more insight into this mechanism.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in TLR4 and TLR2 genes, cytokine production and survival in rural Ghana

et al. 2009

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Toll-like receptors (TLRs) are involved in the induction of an adequate immune response on infection. We hypothesized that genetic variation in TLR4 and TLR2 genes could influence this response and lead to variability in cytokine production and survival. We tested this hypothesis in 4292 participants who were followed up for all-cause mortality for 6 years and live under adverse environmental conditions in the Upper-East region of Ghana, where malaria is endemic. In 605 participants, tumor necrosis factor-a and interleukin-10 (IL10) production, after stimulation with lipopolysaccharide and zymosan, was measured. In addition, 34 single-nucleotide polymorphisms (SNPs) in TLR4 and 12 SNPs in TLR2 were genotyped and tested for association with cytokine production, malaria infection and mortality. In this comprehensive gene-wide approach, we identified novel SNPs in the TLR4 gene that influence cytokine production. From the analyzed SNPs, rs7860896 associated the strongest with IL10 production (P¼0.0005). None of the SNPs in this study associated with malaria or overall mortality risks.In conclusion, we demonstrate that genetic variation within the TLR4 gene influences cytokine production capacity, but in an endemic area does not influence the susceptibility to malaria infection or mortality.

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Regulation of Human Life Histories

Cited by 43 publications

References 80 publications

Interleukin-6 plasma level increases with age in an Italian elderly population (“The Treviso Longeva”–Trelong–study) with a sex-specific contribution of rs1800795 polymorphism

Interleukin-6 plasma level increases with age in an Italian elderly population (“The Treviso Longeva”–Trelong–study) with a sex-specific contribution of rs1800795 polymorphism

The influence of genetic variation on innate immune activation in an environment with high infectious pressure

Polymorphisms in TLR4 and TLR2 genes, cytokine production and survival in rural Ghana

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