VDR and VDBP polymorphisms are associated with 25(OH)D ₃ levels in asthmatic children

Introduction: Serum 25(OH)D 3 is the major circulating metabolite of vitamin D. Vitamin D insufficiency has been associated with asthma susceptibility and severity. Polymorphisms in vitamin D pathway genes have been associated with 25(OH)D 3 levels in other various diseases, not including asthma. Aims: To investigate any association between serum 25(OH)D 3 levels and VDR ApaI, VDBP rs7041 and rs4588 polymorphisms in asthmatic children. Methods: Serum 25(OH)D 3 was measured in 69 asthmatic children and VDR ApaI, VDBP rs7041 and rs4588 SNPs were analyzed using PCR-RFLP method. Asthma control was assessed by Asthma Therapy Assessment Questionnaire (ATAQ). Results: Vitamin D deficiency (25(OH)D 3 ≤20 ng/ml) was associated with not-controlled asthma (ATAQ 3.1±1.5 ng/ml vs 2.0±1.4 ng/ml, p=0.037). Lower serum 25(OH)D 3 levels were associated with the rs7041 TT genotype (18.6±4.7 ng/ml) compared to rs7041 TG and GG genotypes (25.6±2.3 ng/ml and 30.1±12.1, respectively, p=0.006) and the 1f/2 and 2/2 compared to other VDBP diplotypes (p= 0.045). Also, the frequency of rs7041 TT genotype was significantly higher in asthmatic children with 25(OH)D 3 ≤20 ng/ml (35.0%) compared to those with 25(OH)D 3 >20 ng/ml (10.2%, p=0.003). The frequencies of 1f/2, 1f/1s and 2/2 VDBP diplotypes were higher in asthmatic children with 25(OH)D 3 ≤20 ng/ml (20.0% vs 6.3%, 25% vs 2.1% and 40.0% vs 14.6%, respectively, p=0.003). No association was found between serum 25(OH)D 3 and VDR ApaI or VDBP rs4588 genotypes. Discussion: Lower 25(OH)D 3 levels were associated with higher ATAQ score. VDBP rs7041 TT genotype and 1f/2, 1f/1s and 2/2 VDBP diplotypes were found to be associated with lower 25(OH)D 3 serum levels in asthmatic children.