Abstract
BACKGROUND: Potential vitamin D-related influences on inflammatory diseases such as asthma are controversial, including the suggestion that vitamin D insufficiency is associated with increased asthma morbidity. Vitamin D-binding protein transports vitamin D metabolites in the circulation. Single nucleotide polymorphisms in the GC gene encoding vitamin D-binding protein are associated with circulating vitamin D metabolite levels in healthy infants and toddlers. OBJECTIVE: To test the hypothesis that GC single nucleotide polymorphisms encoding the D432E and T436K variants predict subsequent development of asthma in healthy children. METHODS: A retrospective medical record review was performed to determine the development of asthma in 776 children in whom GC genotype, vitamin D-binding protein concentration, and circulating 25-hydroxyvitamin D had been determined at 6 to 36 months of age. Demographic and detailed current clinical data were collected and criteria for asthma were recorded. RESULTS: GC genotype was available for 463 subjects. After an initial analysis of all subject data, the analysis was limited to the predominant Hispanic population (72.1%) to minimize potential confounding effects of ethnicity. Asthma was diagnosed in 87 children (26%). Subjects with the GC genotype encoding the ET/ET (Gc1s/Gc1s) variant had lower odds of developing asthma, representing a protective effect compared with subjects with the DT/DT (Gc1f/Gc1f) variant. CONCLUSION: In the Hispanic population of inner-city New Haven, Connecticut, the ET/ET (Gc1s/Gc1s) genotype of vitamin D-binding protein might confer protection against the development of asthma compared with the wild-type genotype DT/DT (Gc1f/Gc1f).