Associations between Genetic Variants in Vitamin D Metabolism and Asthma Characteristics in Young African Americans: A Pilot Study

Abstract

Introduction Low vitamin D levels have been associated with asthma severity in children. Young, urban African Americans (AA) have high rates of hypovitaminosis D and asthma. Our objective was to determine associations between variants in vitamin D metabolism genes and asthma characteristics in a pilot study of young urban AAs. Materials and Methods Two urban AA cohorts of subjects aged 6 to 20 years (139 subjects with asthma and 74 subjects without asthma) were genotyped for 12 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). In a case-control analysis, SNPs were studied for associations with an asthma diagnosis. Within the asthmatic cohort, SNPs were analyzed for associations with quantitative asthma characteristics. All analyses were adjusted for age, gender, and BMI percentile. Results Only the CYP2R1 SNP rs10766197 homozygous minor genotype was associated with asthma (P=0.044). CYP24A1 SNP rs2248137 was associated with lower vitamin D levels (P=0.006). Within the asthma cohort, multiple significant associations between SNPs and asthma characteristics were identified; VDR SNP rs2228570 was associated with the higher nighttime asthma morbidity scores (P=0.04), lower baseline spirometric measures (P<0.05), ≥1 positive aeroallergen skin test (P=0.003), and increased IgE levels (P<0.001). Discussion This pilot study demonstrates that variants in vitamin D metabolism genes are associated with quantitative asthma characteristics in young, urban AAs. The collection of these associations provides evidence for the need for a large population-based study of vitamin D relevant SNPs in this cohort.

Impact of Vitamin D Receptor VDR rs2228570 Polymorphism in Oldest Old

“…The known influence of VDR on the immune response [6,7,8] may have contributed to or even accounted for the impact of the VDR rs2228570 polymorphism on allergy. Previous observations revealed an influence of the FokI VDR polymorphism on prevalance and/or clinical course of asthma [27,28], immune type 1 diabetes [77], multiple sclerosis [31], systemic lupus erythematosus [78], graft rejection [79], ulcerative colitis [40], aggressive periodontitis [30] and dengue hemorrhagic fever [80]. …”

“…Polymorphisms of VDR have been reported to be associated with bone mineral density [23] diabetes mellitus [24,25], hypertension [26], asthma [27,28], periodontitis [29,30], risk of multiple sclerosis [31,32] and malignancy [33,34,35,36,37,38]. On the other hand, several studies failed to report an impact of VDR polymorphisms on multiple sclerosis [39], inflammatory bowel disease [40], coronary artery disease [41] or malignancy [42,43,44].…”

Cytochromes P450 and Skin Cancer: Role of Local Endocrine Pathways

“…On the other hand, a recent study [213] on a group of 305 patients with histopathologically confirmed melanoma found no correlation between SNPs in CYP27B1 (rs4646536), CYP24A1 (rs927650), vitamin D binding protein VDBP (rs1155563, rs7041) and melanoma risk [213]. Other studies indicated an association of CYP24A1 SNP (rs2248137) with lower vitamin D levels, and the CYP2R1 SNP (rs10766197) was linked to asthma [215]. Another study confirmed association between three SNPs in CYP27B1 and multiple sclerosis [216].…”

The impact of vitamin D on asthmatic human airway smooth muscle

“…Examination of single nucleotide polymorphisms (SNPs) in genes involved with vitamin D metabolism and signaling, particularly CYP24A1 (the main enzyme to degrade 1,25(OH) 2 D 3 ), have shown that there is a heritable component of the vitamin D status in families with asthma [15,16]. Vitamin D deficiency is believed to contribute to asthma pathogenesis by promoting steroid resistance, AHR and airway remodeling [17,18].…”