Genetic variations in Vitamin D Binding Protein (VDBP) impact vitamin D level and asthma susceptibility across the four ethnic populations

BACKGROUND: Asthma are associated with the vitamin D axis. Genetic variations of VDBP, notably rs7041 and rs4588, influence circulating vitamin D levels. However, data on their link to asthma are inconsistent, and ethnic differences remain unclear. OBJECTIVE: We explored how genetic variations in VDBP affect vitamin D levels and susceptibility to asthma across diverse ethnic populations. METHODS: In our cross-ethnic study, we analyzed vitamin D levels and VDBP polymorphisms (rs7041 and rs4588) in Taiwanese, Mongolian, Lithuanian, and Latvian populations. Our study included 363 asthmatic subjects and 481 non-asthma controls. We performed genotyping for rs7041 and rs4588 and assessed serum concentrations of 25-hydroxyvitamin D [25(OH)D], examining the associations between VDBP polymorphisms, vitamin D levels, and asthma. RESULTS: The study found significant differences in vitamin D levels among ethnic groups. Non-asthmatic individuals from Taiwan had higher concentrations, while asthma subjects in both Taiwanese and Lithuanian populations showed lower levels compared to their non-asthma counterparts (both p-value < 0.001). VDBP polymorphisms were associated with asthma in the Latvian population, with the rs7041 GG vs. GT+TT showing an odds ratio (OR) of 1.72 (95% confidence interval (CI): 1.10-2.69, p = 0.016) and the rs4588 CC vs. CA+AA showing an OR of 1.88 (95%CI: 1.24-2.84, p = 0.003). However, this association was not observed in other populations. CONCLUSIONS: Our cross-ethnic study underscores the intricate relationship between VDBP genetic variations, vitamin D levels, and asthma vulnerability. The association of VDBP polymorphisms with asthma seems to differ among populations, emphasizing the importance of a nuanced comprehension of these connections.