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Experimental Biology 2010: Associations Between Genetic Variants In Vitamin D Metabolism And Asthma Phenotype Traits In Young African Americans
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Associations Between Genetic Variants In Vitamin D Metabolism And Asthma Phenotype Traits In Young African Americans
D. Pillai1,2, S.F. Iqbal1,2, A.S. Benton1,2, T. Ozerdirne3, H. Holbrook1, S.J. Teach2, R.J. Freishtat1,2 1 Department of Integrative Systems Biology, Children's National Medical Center, Washington, DC 2 School of Medicine and Health Sciences, George Washington University, Washington, DC 3 University of California at Davis, Davis, CA
Purpose of Study: Low vitamin D levels have been associated with asthma severity in children. Urban African Americans (AA) have high rates of hypovitaminosis D and asthma, yet no study has assessed the relationship between variants in vitamin D metabolism genes and asthma phenotype traits in this population. Our goal was to identify associations between genetic variants in vitamin D metabolism genes and quantitative asthma phenotype traits in a young, urban African American population. Methods Used: In a cross-sectional study, urban AA cohorts of 139 subjects with asthma (6 to 20 yrs) and 74 subjects without asthma (6 to 19 yrs) were genotyped for 12 candidate single nucleotide polymorphisms (SNPs) in 3 vitamin D metabolism genes: VDR (vitamin D receptor), CYP24A1 (cytochrome P450 vitamin D 24-hydroxylase), and CYP2R1 (cytochrome P450 vitamin D 25-hydroxylase). After adjusting for age, gender, and BMI percentile, SNPs were analyzed for associations with the diagnosis of asthma. Within the asthma cohort, SNPs were analyzed for associations with quantitative measures of asthma phenotype traits including spirometry, blood eosinophils (%), and asthma severity scores. Summary of Results: Only the AA genotype for CYP2R1 SNP rs10766197 was associated with the diagnosis of asthma (P=0.044). In the asthma cohort, multiple SNP associations were identified with quantitative asthma phenotype traits. For example, CYP24A1 SNP rs2248137 was associated with lower vitamin D levels (P=0.006) and a decreased bronchodilator response based on change in FEV1/FVC (P=0.007). Additionally, VDR SNP rs2228570 was associated with the presence of >1 positive aeroallergen skin test (P=0.003), increased serum IgE levels (P<0.001), higher nighttime morbidity scores (P=0.04), and lower baseline spirometric measures (P<0.05). Conclusions: This is the first study demonstrating that variants in genes responsible for vitamin D metabolism are associated with quantitative asthma phenotype traits in a young, urban AA cohort. The abundance of such associations supports the importance of vitamin D metabolism in asthma within this population.
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