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

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.

To determine whether the tumor necrosis factor (TNF) G-308A genotype influences the risk for respiratory illness-related school absences associated with SHS exposure.

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.

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.

These results indicate that a subgroup of genetically susceptible children are at substantially greater risk of respiratory illness if exposed to SHS.