Genetic Diversity in Bronchial Asthma Susceptibility: Exploring the Role of Vitamin D Receptor Gene Polymorphisms in Varied Geographic Contexts

支气管哮喘易感性的遗传多样性:探索维生素 D 受体基因多态性在不同地理环境中的作用

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作者:Natalia Paramonova, Ilva Trapina, Brigita Gradauskiene Sitkauskiene, Samanta Plavina, Laura Tamasauskiene, Daina Bastyte, Ingrida Rumba-Rozenfelde, Sandra Tapina, Ieva Stakaitiene, Rasa Ugenskiene, Lawrence Shih-Hsin Wu, Jiu-Yao Wang, Miao-Hsi Hsieh, Pei-Chi Chen, Nikolajs Sjakste

Abstract

Bronchial asthma (BA) exhibits varying prevalence across global populations, prompting a comprehensive investigation into genetic and environmental determinants. Vitamin D is a potent immunomodulator capable of suppressing inflammatory signals in several cell types involved in the asthmatic response; it exerts effects on the immune system by binding to the nuclear vitamin D receptor (VDR). VDR gene genetic variations are affecting serum vitamin D levels with a possible role in the BA risk. The current study aimed to examine the complex interaction of various factors (genetic background, serum vitamin D levels, and geographic location) to identify differences in the influence of these factors on the susceptibility to asthma between populations at different latitudes. Focusing on Eastern European cohorts from Latvia and Lithuania and comparing them with published data on East Asian populations, we explore the impact of VDR gene polymorphisms on BA susceptibility. Genotyping four key VDR SNPs and assessing their association with 25-hydroxyvitamin D levels, our study unveils significant associations of the studied loci with the risk of asthma-both risk-reducing and increasing effects, differently distributed between Baltic and East Asian populations. The functional effects of in silico VDR gene genetic variations are also identified and discussed.

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