Selection for Genetic Variation Inducing Pro-Inflammatory Responses under Adverse Environmental Conditions in a Ghanaian Population

Kuningas, Maris; May, Linda; Tamm, Riin; Bodegom, David van; Biggelaar, Anita H. J. van den; Meij, Johannes J.; Frölich, Marijke; Ziem, Juventus B.; Suchiman, H. Eka D.; Metspalu, Andres; Slagboom, P. Eline; Westendorp, Rudi G. J.

doi:10.1371/journal.pone.0007795

Cited by 39 publications

(62 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although a full exploration of the possible evolutionary mechanisms of this observation are beyond the scope this report, it is interesting to note that studies of other interleukin genes such as IL-10 have suggested that natural selection may be acting on proinflammatory haplotypes within the peoples of sub-Saharan Africa and Caucasians. 18 In addition, contrary to our expectations, we observed significantly higher gene diversity indices in the European populations when compared with the African populations at three tSNPs and at the haplotype level. It is likely that this is a result of the tSNPs used here being ascertained in European samples, and that with analysis of full resequencing data, we would observe higher genetic diversity in the African populations.…”

Section: Discussioncontrasting

confidence: 99%

The frequency of an IL-18-associated haplotype in Africans

Thompson¹,

Humphries

Thomas

et al. 2012

Eur J Hum Genet

View full text Add to dashboard Cite

Variation within the gene for the proinflammatory cytokine interleukin (IL)-18 has been associated with inter-individual differences in levels of free protein and disease risk. We investigated the frequency of function-associated IL18 gene haplotypes in an extensive sample (n ¼ 2357) of African populations from across the continent. A previously identified five tagging SNP (single-nucleotide polymorphism) haplotype (here designated hGTATA), known to be associated with lower levels of IL-18, was observed at a frequency of 27% in a British population of recent European ancestry, but was found at low frequency (o8%) or completely absent in African populations. Potentially protective variants may, as a consequence, be found at low frequency in African individuals and may confer a difference in disease risk.

show abstract

Section: Discussioncontrasting

confidence: 99%

The frequency of an IL-18-associated haplotype in Africans

Thompson¹,

Humphries

Thomas

et al. 2012

Eur J Hum Genet

View full text Add to dashboard Cite

show abstract

“…Carriers of haplotype 1 had a decreased IL-10 and an increased TNF-a production upon stimulation with Escherichia coli lipopolysaccharide (LPS) and Saccharomyces cerevisiae zymosan. This haplotype was thus associated with a pro-inflammatory innate immune response and was subsequently shown to be enriched among elderly members of the population, 7 which is in line with a survival benefit with more pro-inflammatory responses.…”

Section: Introductionmentioning

confidence: 79%

“…Third, we previously re-sequenced the IL10 gene beyond linkage disequilibrium boundaries and did not reveal any other variants in haplotype 1 than the four previously mentioned SNPs, which would suggest that one or more of these SNPs is a functional variant. 7 The most likely candidates would be SNPs rs1800871 and rs1800872 as they lie in the promoter region of the IL10 gene, while rs3024490 and rs1554286 lie in intron regions of the gene.…”

Section: Discussionmentioning

confidence: 99%

“…7 The pro-inflammatory cytokine TNF-a can stimulate production of IL-10, 8 which has antiinflammatory properties and inhibits production of proinflammatory cytokines including TNF-a. 9 Because of the regulatory effect of IL-10 on pro-inflammatory cytokine production, the effect of genetic variation in the IL10 gene on TNF-a production was also investigated.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2011

View full text Add to dashboard Cite

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.

show abstract

“…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.…”

Section: Communicable Diseasesmentioning

confidence: 99%

Cardiovascular risk factors in sub-Saharan Africa: a review

Monti¹,

Ruggieri²,

Vincentelli

et al. 2015

Ital J Med

View full text Add to dashboard Cite

Ischemic heart disease is increasing dramatically in the Sub-Saharan Africa (SSA), despite an increasing prevalence of risk factors, and some characteristics of the African people that make the African population subject to the effects of major cardiovascular risk factors. The pace and direction of economic development, rates of urbanization, the changes in life expectancy, associated with different pathophysiological factors are causing an increased rate of atherosclerotic disease in these countries. The prevalence of ischemic heart disease in SSA has shown a significant rise in the next two following decades due to the rising prevalence of risk factors, especially hypertension, diabetes, overweight and obesity, physical inactivity, tobacco use and the dyslipidemia, mainly due to an increase in urbanization. Moreover, thanks to new knowledge, it has been pointed out the difference of individual risk factors in the African population and other populations due to genetic differences. It is estimated that age-standardized approach for ischemic heart disease mortality rates will rise by 27% in African men and 25% in women by 2015 and by 70 and 74%, respectively by 2030. More research is needed in Africa to provide evidence for cardiovascular prevention and treatment to mitigate the oncoming epidemic. Health interventions are needed for preventing or reducing the morbidity/mortality and should be addressed to both children and adults, including score of the risk stratification modified, starting early and aggressive therapy, if necessary.

show abstract

Selection for Genetic Variation Inducing Pro-Inflammatory Responses under Adverse Environmental Conditions in a Ghanaian Population

Cited by 39 publications

References 34 publications

The frequency of an IL-18-associated haplotype in Africans

The frequency of an IL-18-associated haplotype in Africans

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

Cardiovascular risk factors in sub-Saharan Africa: a review

Contact Info

Product

Resources

About