TNF-308 modifies the effect of second-hand smoke on respiratory illness-related school absences.

RATIONALE: Exposure to second-hand smoke (SHS) has been associated with increased risk of respiratory illness in children including respiratory illness-related school absences. The role of genetic susceptibility in risk for adverse effects from SHS has not been extensively investigated in children. OBJECTIVE: To determine whether the tumor necrosis factor (TNF) G-308A genotype influences the risk for respiratory illness-related school absences associated with SHS exposure. METHODS: Incident school absences were collected, using an active surveillance system, between January and June 1996, as part of the Air Pollution and Absence Study, a prospective cohort study nested in the Children's Health Study. Buccal cells and absence reports were collected on 1,351 students from 27 elementary schools in California. MEASUREMENTS AND MAIN RESULTS: Illness-related school absences were classified as nonrespiratory and respiratory illness-related, which were further categorized into upper or lower respiratory illness-related absences based on symptoms. The effect of SHS exposure on respiratory illness-related absences differed by TNF genotype (p interaction, 0.02). In children possessing at least one copy of the TNF-308 A variant, exposure to two or more household smokers was associated with a twofold risk of a school absence due to respiratory illness (relative risk, 2.13; 95% confidence interval, 1.34, 3.40) and a fourfold risk of lower respiratory illness-related school absence (relative risk, 4.15; 95% confidence interval, 2.57, 6.71) compared with unexposed children homozygous for the common TNF-308 G allele. CONCLUSIONS: These results indicate that a subgroup of genetically susceptible children are at substantially greater risk of respiratory illness if exposed to SHS.