Neighborhood disadvantage and elevated CD14 gene expression among middle-aged adults: Findings from the Midlife in...

Social and environmental factors are crucial in health, partly through immune system programming that begins decades before chronic disease onset. This study quantified the associations between neighborhood opportunity and CD14 gene expression, a key marker of monocyte abundance and inflammatory potential in the circulating leukocyte pool. Neighborhood opportunity was measured using the Childhood Opportunity Index 3.0 reflecting Overall Neighborhood Opportunity and three subdomains (Education, Health and Environment, and Social and Economic Resources). Multivariable linear regression analyses among 1215 middle-aged adults (57 ± 12 years) from the Midlife in the United States Study revealed that individuals residing in disadvantaged neighborhoods had 36.6 % (95 % CI: 11.7-65.9 % elevation, p = 0.002) higher CD14 gene expression levels than those in neighborhoods with high opportunity, even after adjusting for key sociodemographic characteristics and health behaviors. The Education domain (27.5 % elevation, 95 % CI: 5.0-54.8 % elevation, p = 0.015) and Social & Economic Resources domain (32.9 % elevation, 95 % CI: 8.7-62.5 % elevation, p = 0.006) strongly tracked with elevated CD14 gene expression levels. These findings extend previous research showing how social factors "get under the skin" through sympathetic nervous system activation and altered myelopoiesis, producing a proinflammatory, glucocorticoid-resistant immune phenotype.