Association Between Single Nucleotide Polymorphisms Related to Vitamin D Metabolism and the Risk of Developing Asthma

Overview

Journal Nutrients

Date 2023 Feb 25

PMID 36839181

Authors

Susana Rojo-Tolosa

Laura Elena Pineda-Lancheros

Jose Maria Galvez-Navas

Jose Antonio Sanchez-Martinez

Maria Victoria Gonzalez-Gutierrez

Andrea Fernandez-Alonso

Concepcion Morales-Garcia

Alberto Jimenez-Morales

Cristina Perez-Ramirez

Affiliations

Soon will be listed here.

Abstract

Asthma is a chronic non-communicable disease that affects all age groups. The main challenge this condition poses is its heterogeneity. The role of vitamin D in asthma has aroused great interest, correlating low vitamin D levels and polymorphisms in the genes involved in its metabolic pathway with the risk of asthma. The aim of this study was to evaluate the influence of 13 single nucleotide polymorphisms (SNPs) related to the vitamin D metabolism on the susceptibility to asthma. An observational case-control study was performed, including 221 patients with asthma and 442 controls of Caucasian origin from southern Spain. The SNPs (rs6068816, rs4809957), (rs10877012, rs4646536, rs703842, rs3782130), (rs7041), (rs10741657) and (ApaI, BsmI, FokI, Cdx2, TaqI) were analyzed by real-time PCR, using TaqMan probes. The logistic regression model adjusted for body mass index revealed that in the genotype model, carriers of the Cdx2 rs11568820-AA genotype were associated with a higher risk of developing asthma ( = 0.005; OR = 2.73; 95% CI = 1.36-5.67; AA vs. GG). This association was maintained in the recessive model ( = 0.004). The haplotype analysis revealed an association between the ACTATGG haplotype and higher risk of asthma for the rs1544410, rs7975232, rs731236, rs4646536, rs703842, rs3782130 and rs10877012 genetic polymorphisms ( = 0.039). The other SNPs showed no effect on risk of developing asthma. The Cdx2 polymorphism was significantly associated with the susceptibility of asthma and could substantially act as a predictive biomarker of the disease.

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References

Latacz M, Snarska J, Kostyra E, Fiedorowicz E, Savelkoul H, Grzybowski R . Single Nucleotide Polymorphisms in 25-Hydroxyvitamin D3 1-Alpha-Hydroxylase ( Gene: The Risk of Malignant Tumors and Other Chronic Diseases. Nutrients. 2020; 12(3). PMC: 7146376. DOI: 10.3390/nu12030801. View

Navas-Nazario A, Li F, Shabanova V, Weiss P, Cole D, Carpenter T . Effect of vitamin D-binding protein genotype on the development of asthma in children. Ann Allergy Asthma Immunol. 2014; 112(6):519-24. PMC: 4070170. DOI: 10.1016/j.anai.2014.03.017. View

Rochel N . Vitamin D and Its Receptor from a Structural Perspective. Nutrients. 2022; 14(14). PMC: 9325172. DOI: 10.3390/nu14142847. View

Sassi F, Tamone C, DAmelio P . Vitamin D: Nutrient, Hormone, and Immunomodulator. Nutrients. 2018; 10(11). PMC: 6266123. DOI: 10.3390/nu10111656. View

Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira M, Bender D . PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007; 81(3):559-75. PMC: 1950838. DOI: 10.1086/519795. View

Caminati M, Pham D, Bagnasco D, Canonica G . Type 2 immunity in asthma. World Allergy Organ J. 2018; 11(1):13. PMC: 6020328. DOI: 10.1186/s40413-018-0192-5. View

Wjst M . Variants in the vitamin D receptor gene and asthma. BMC Genet. 2005; 6:2. PMC: 546000. DOI: 10.1186/1471-2156-6-2. View

Bikle D . Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol. 2014; 21(3):319-29. PMC: 3968073. DOI: 10.1016/j.chembiol.2013.12.016. View

Ohyama Y, Noshiro M, Okuda K . Cloning and expression of cDNA encoding 25-hydroxyvitamin D3 24-hydroxylase. FEBS Lett. 1991; 278(2):195-8. DOI: 10.1016/0014-5793(91)80115-j. View

10.

Yang F, Bergeron J, Linehan L, Lalley P, Sakaguchi A, BOWMAN B . Mapping and conservation of the group-specific component gene in mouse. Genomics. 1990; 7(4):509-16. DOI: 10.1016/0888-7543(90)90193-x. View

11.

Munkhbayarlakh S, Kao H, Hou Y, Tuvshintur N, Bayar-Ulzii B, Narantsetseg L . Vitamin D plasma concentration and vitamin D receptor genetic variants confer risk of asthma: A comparison study of Taiwanese and Mongolian populations. World Allergy Organ J. 2019; 12(11):100076. PMC: 6838943. DOI: 10.1016/j.waojou.2019.100076. View

12.

Uitterlinden A, Fang Y, van Meurs J, Pols H, van Leeuwen J . Genetics and biology of vitamin D receptor polymorphisms. Gene. 2004; 338(2):143-56. DOI: 10.1016/j.gene.2004.05.014. View

13.

Bosse Y, Lemire M, Poon A, Daley D, He J, Sandford A . Asthma and genes encoding components of the vitamin D pathway. Respir Res. 2009; 10:98. PMC: 2779188. DOI: 10.1186/1465-9921-10-98. View

14.

Gonzalez Rojo P, Perez Ramirez C, Galvez Navas J, Pineda Lancheros L, Rojo Tolosa S, Ramirez Tortosa M . Vitamin D-Related Single Nucleotide Polymorphisms as Risk Biomarker of Cardiovascular Disease. Int J Mol Sci. 2022; 23(15). PMC: 9368814. DOI: 10.3390/ijms23158686. View

15.

Zhang Y, Zhang L, Chen S, Yang G, Huang X, Duan Y . Association between VDR polymorphisms and multiple sclerosis: systematic review and updated meta-analysis of case-control studies. Neurol Sci. 2017; 39(2):225-234. DOI: 10.1007/s10072-017-3175-3. View

16.

Jolliffe D, Greiller C, Mein C, Hoti M, Bakhsoliani E, Telcian A . Vitamin D receptor genotype influences risk of upper respiratory infection. Br J Nutr. 2018; 120(8):891-900. DOI: 10.1017/S000711451800209X. View

17.

Kuruvilla M, Vanijcharoenkarn K, Shih J, Lee F . Epidemiology and risk factors for asthma. Respir Med. 2019; 149:16-22. DOI: 10.1016/j.rmed.2019.01.014. View

18.

Alcantara Galvao A, de Araujo Sena F, de Andrade Belitardo E, de Santana M, Costa G, Cruz A . Genetic polymorphisms in vitamin D pathway influence 25(OH)D levels and are associated with atopy and asthma. Allergy Asthma Clin Immunol. 2020; 16:62. PMC: 7386242. DOI: 10.1186/s13223-020-00460-y. View

19.

Saadi A, Gao G, Li H, Wei C, Gong Y, Liu Q . Association study between vitamin D receptor gene polymorphisms and asthma in the Chinese Han population: a case-control study. BMC Med Genet. 2009; 10:71. PMC: 2720948. DOI: 10.1186/1471-2350-10-71. View

20.

Toledano J, Moreno-Fernandez J, Puche-Juarez M, Ochoa J, Diaz-Castro J . Implications of Vitamins in COVID-19 Prevention and Treatment through Immunomodulatory and Anti-Oxidative Mechanisms. Antioxidants (Basel). 2022; 11(1). PMC: 8773198. DOI: 10.3390/antiox11010005. View