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

Abstract

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.

Variants of the IL‐10 gene associate with muscle strength in elderly from rural Africa: a candidate gene study

“…It has been previously shown that several single nucleotide polymorphisms (SNPs) in the IL-10 gene region influence the production capacities of IL-10 and TNF-α measured in two independent groups in 2006 and 2008 in this research area (Kuningas et al ., 2009; Boef et al ., 2012). First, we confirmed that these relations were present in 1177 individuals of whom IL-10 gene variants were known and of whom measurements of cytokine production capacities were combined from 2005, 2006 and 2008 (Fig.…”

“…It has been previously shown that the SNPs in the IL-10 gene region constitute two haplotypes that influence the production capacities of IL-10 and TNF-α: a pro-inflammatory haplotype 1 and an anti-inflammatory haplotype 3 (Kuningas et al ., 2009; Boef et al ., 2012). We reanalysed the relation between the haplotypes of the IL-10 gene and cytokine production capacities in the 1177 individuals of whom IL-10 gene variants were known and of whom measurements of cytokine production capacities were combined from 2005, 2006 and 2008.…”

“…We have earlier reported that specific IL-10 gene variants are enriched in Ghanaian elderly living under adverse conditions (Kuningas et al ., 2009). These variants have functional significance: some are related to a pro-inflammatory cytokine production capacity, with lower IL-10 and higher TNF-α levels upon whole-blood stimulation with LPS, while others are related to an inverse anti-inflammatory response (Kuningas et al ., 2009; May et al ., 2009b; Boef et al ., 2012). Interestingly, this IL-10 haplotype structure is less present in Caucasian populations living under affluent conditions (Moraes et al ., 2003; Kuningas et al ., 2009), possibly because balanced selection has conserved this haplotype structure in populations under adverse conditions.…”

“…For this study, we had the unique opportunity to study handgrip strength of individuals aged 50 years and older in the Ghanaian population of which we have extensively characterized the IL-10 gene variants and their effects on cytokine production capacity (Kuningas et al ., 2009; May et al ., 2009b; Boef et al ., 2012). This study aims to investigate the relation between the pro- and anti-inflammatory IL-10 gene variants, which are not present in Caucasian populations, and handgrip strength as a proxy of overall muscle strength.…”

Cardiovascular risk factors in sub-Saharan Africa: a review

“…73,74 This means that the activated macrophages stimulate both local lipid accumulation and the instability that presages plaque rupture. [75][76][77] Coronary heart disease IHD remains relatively uncommon in SSA despite an increasing prevalence of risk factors but its incidence is rising. A study of the 1954 have been evidenced by 3500 postmortem studies in Ghana in which only three cases of CHD were found.…”