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

Miao-Hsi Hsieh,¹ Natalia Paramonova,² Brigita Gradauskiene (Sitkauskiene),³ Ilva Trapina,² Ingrida Rumba-Rozenfelde,⁴ Sonomjamts Munkhbayarlakh,⁵ Samanta Plavina,² Nikolajs Sjakste,² Daina Bastyte,³ Laura Tamasauskiene,³ Ieva Stakaitiene,⁶ Rasa Ugenskiene,⁶ Pei-Chi Chen,^1,7 Jiu-Yao Wang,^1,8 Lawrence Shih-Hsin Wu^1,9

Affiliations:
¹ Research Center of Allergy, Immunology, and Microbiome (A.I.M.), China Medical University Hospital, Taichung, Taiwan
² Laboratory of Genomics and Bioinformatics, Institute of Biology, University of Latvia, Riga, Latvia
³ Department of Immunology and Allergology, Lithuanian University of Health Sciences, Kaunas, Lithuania
⁴ Faculty of Medicine, University of Latvia, Riga, Latvia;
⁵ Department of Pulmonology and Allergology, School of Medicine, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
⁶ Department of Genetics and Molecular Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania
⁷ Department of Nursing, National Tainan Junior College of Nursing, Tainan, Taiwan
⁸ Department of Allergy and Immunology, China Medical University Children’s Hospital, Taichung, Taiwan
⁹ Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

Abstract

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.
Conclusion: 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.
Key words: vitamin D, vitamin D binding protein, genetic polymorphism, asthma, cross-ethnic comparison