Selection for genetic variation inducing pro-inflammatory responses under adverse environmental conditions in a Ghanaian population

Background: Chronic inflammation is involved in the pathogenesis of chronic age-associated, degenerative diseases. Proinflammatoryhost responses that are deleterious later in life may originate from evolutionary selection for genetic variationmediating resistance to infectious diseases under adverse environmental conditions.Methodology/Principal Findings: In the Upper-East region of Ghana where infection has remained the leading cause ofdeath, we studied the effect on survival of genetic variations at the IL10 gene locus that have been associated with chronicdiseases. Here we show that an IL10 haplotype that associated with a pro-inflammatory innate immune response,characterised by low IL-10 (p = 0.028) and high TNF-a levels (p = 1.3961023), was enriched among Ghanaian elders(p = 2.4661026). Furthermore, in an environment where the source of drinking water (wells/rivers vs. boreholes) influencesmortality risks (HR 1.28, 95% CI [1.09–1.50]), we observed that carriers of the pro-inflammatory haplotype have a survivaladvantage when drinking from wells/rivers but a disadvantage when drinking from boreholes (pinteraction = 0.013).Resequencing the IL10 gene region did not uncover any additional common variants in the pro-inflammatory haplotype tothose SNPs that were initially genotyped.Conclusions/Significance: Altogether, these data lend strong arguments for the selection of pro-inflammatory hostresponses to overcome fatal infection and promote survival in adverse environments.