Abstract
Rationale: Single nucleotide polymorphisms in the region of gasdermin-like (GSDML) gene on chromosome 17q12-21 are associated with increased risks of childhood-onset asthma. These risks seem to be modified by environmental tobacco smoke.
Objectives: To assess whether the associations of GSDML with asthma-like symptoms are modified by smoke exposure, both during fetal and in early life.
Methods: This study was embedded in the Generation R Study, a population-based prospective cohort study from fetal life onwards in the Netherlands. We genotyped GSDML (rs2305480) and assessed maternal smoking repeatedly during pregnancy and smoke exposure in early life at the age of 2 years by questionnaires. Asthma-like symptoms were reported by parents at the ages of 1, 2, 3 and 4 years. The analyses were based on 2,025 Caucasian children with complete data.
Results: GSDML was associated with asthma-like symptoms at the ages of 2, 3 and 4 years (overall Odds Ratio 1.15 (1.06, 1.26)). The GSDML effect on asthma-like symptoms was stronger among children who were exposed to smoke during fetal life (p interaction=0.030). Smoke exposure in early life also tended to increase the effect of GSDML on asthma-like symptoms, but the test for interaction was not significant (p interaction=0.240). The modifying effects by fetal and smoke exposure in early life were independent. The strongest effects were present in children aged 3 and 4 years with both the risk-allele and smoke exposure during fetal and early life.
Conclusion: GSDML is associated with asthma-like symptoms in preschool children, and this association seems to be modified by fetal and smoke exposure in early life.
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