Antagonistic Pleiotropy at the Human IL6 Promoter Confers Genetic Resilience to the Pro-Inflammatory Effects of Adverse Social Conditions in Adolescence

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 -174 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.