title: Antagonistic pleiotropy at the human IL6 promoter confers genetic resilience to the pro-inflammatory effects of adverse social conditions in adolescence.
abstract: The authors tested the evolutionary genetic hypothesis that the functional form of an asymmetrically risky Gene × Environment interaction will differ as a function of age-related antagonistic pleiotropy (i.e., show opposite effects in young vs. old individuals). Previous studies have identified a polymorphism in the human IL6 promoter (rs1800795; IL6-74 G/C) that interacts with adverse socioenvironmental conditions to promote chronic inflammation in older adults (elevated C-reactive protein). This study identifies a protective effect of the same polymorphism in 17- to 19-year-old adolescents confronting socioeconomic adversity. Over 60% of the environmental risk contribution to the IL6 × Socioeconomic Status interaction could be accounted for by interpersonal stress and adult role burden. Thus, the IL6-174G allele does not represent an undifferentiated risk factor but instead sensitizes inflammatory biology to socioenvironmental conditions, conferring either genetic vulnerability or resilience depending on the developmental "somatic environment" that interacts with social conditions to influence gene expression.
authors.affiliation: Department of Medicine, Norman Cousins Center, Jonsson Comprehensive Cancer Center, Molecular Biology Institute, University of California, Los Angeles, CA, USA. coles@ucla.edu
authors.forename: Steven W
authors.initials: SW
authors.lastname: Cole
authors.forename: Jesusa M G
authors.initials: JM
authors.lastname: Arevalo
authors.forename: Kavya
authors.initials: K
authors.lastname: Manu
authors.forename: Eva H
authors.initials: EH
authors.lastname: Telzer
authors.forename: Lisa
authors.initials: L
authors.lastname: Kiang
authors.forename: Julienne E
authors.initials: JE
authors.lastname: Bower
authors.forename: Michael R
authors.initials: MR
authors.lastname: Irwin
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Fuligni
mesh_terms: D000293:Adolescent; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D012923:Social Class; D012931:Social Environment; D055815:Young Adult
chemical_list: D015850:Interleukin-6; D002097:C-Reactive Protein