title: Selection for genetic variation inducing pro-inflammatory responses under adverse environmental conditions in a Ghanaian population.
abstract: BACKGROUND
  Chronic inflammation is involved in the pathogenesis of chronic age-associated, degenerative diseases. Pro-inflammatory host responses that are deleterious later in life may originate from evolutionary selection for genetic variation mediating resistance to infectious diseases under adverse environmental conditions.
  
  
  RESULTS
  In the Upper-East region of Ghana where infection has remained the leading cause of death, we studied the effect on survival of genetic variations at the IL10 gene locus that have been associated with chronic diseases. 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-alpha levels (p = 1.39 x 10(-3)), was enriched among Ghanaian elders (p = 2.46 x 10(-6)). Furthermore, in an environment where the source of drinking water (wells/rivers vs. boreholes) influences mortality risks (HR 1.28, 95% CI [1.09-1.50]), we observed that carriers of the pro-inflammatory haplotype have a survival advantage when drinking from wells/rivers but a disadvantage when drinking from boreholes (p(interaction) = 0.013). Resequencing the IL10 gene region did not uncover any additional common variants in the pro-inflammatory haplotype to those SNPs that were initially genotyped.
  
  
  CONCLUSIONS
  Altogether, these data lend strong arguments for the selection of pro-inflammatory host responses to overcome fatal infection and promote survival in adverse environments.
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Maris
authors.initials: M
authors.lastname: Kuningas
authors.forename: Linda
authors.initials: L
authors.lastname: May
authors.forename: Riin
authors.initials: R
authors.lastname: Tamm
authors.forename: David
authors.initials: D
authors.lastname: van Bodegom
authors.forename: Anita H J
authors.initials: AH
authors.lastname: van den Biggelaar
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Meij
authors.forename: Marijke
authors.initials: M
authors.lastname: Frölich
authors.forename: Juventus B
authors.initials: JB
authors.lastname: Ziem
authors.forename: Helena E D
authors.initials: HE
authors.lastname: Suchiman
authors.forename: Andres
authors.initials: A
authors.lastname: Metspalu
authors.forename: P Eline
authors.initials: PE
authors.lastname: Slagboom
authors.forename: Rudi G J
authors.initials: RG
authors.lastname: Westendorp
mesh_terms: D000375:Aging; D000483:Alleles; D004777:Environment; D014644:Genetic Variation; D005838:Genotype; D005869:Ghana; D006239:Haplotypes; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000235:genetics*; D016753:Interleukin-10 / Q000235:genetics*; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10