Association of vitamin D gene polymorphisms in children with asthma - A systematic review

Abstract

Introduction The association of Vitamin D and children with asthma is known and there are several individual studies on Vitamin D polymorphisms. However, systematic reviews on all vitamin D associated gene polymorphisms have not been done in children with asthma. Objective To investigate the association of Vitamin D associated gene polymorphisms and asthma in children (0–18 years) by systematic review and meta-analytic approach. Methods Our search included 20 full text articles of which 15 were case control studies and 5 used family based linkage disequilibrium method. Total of 2491cases and 3682 controls were included in case control studies, with mean age of 9.58 years and 10.16 years respectively. Quantitative and qualitative analysis were done. Results Quantitative analysis revealed significant association with protective effect of Apa1 polymorphism in allele (OR 0.81 (0.71,0.91) and homozygous major form (OR 0.83 (0.70,0.98) and Taq 1 minor allele in homozygous form (OR 0.73 (0.58,0.92) in children with asthma. However, the minor allele of Apa1(OR 1.21 (1.07,1.37), Bsm 1 in heterozygous (OR 1.35 (1.07,1.71) and homozygous minor form (OR 1.95 (1.59,2.39), major allele of Fok1(OR1.34 (1.17,1.52) and Taq1 (OR 1.22 (1.08,1.38) were found to be increasing the odds of asthma. Ethnic variations were noted in subgroup analysis. Qualitative analysis of the polymorphisms of the Vitamin D associated metabolic genes also showed significant associations. Conclusion Our review shows significant associations with VDR polymorphisms - Apa1, Bsm1, Fok 1, Taq 1, polymorphisms of Vitamin D metabolic genes – CYP27A1, CYP 2R1, CYP 24A1, GC and genes related to Vitamin D response element (VDRE) in children with asthma. Conducting large studies involving various ethnic regions will strengthen our knowledge on the association and aid in targeted interventions for control of asthma in children.

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

“…In our study, the presence of CYP2R1 rs10741657 was not related to a higher risk of suffering from asthma. Similarly, previous studies conducted in a Caucasian population (n = 154 cases/154 controls) and a Caucasian pediatric population (n = 1386 cases/1305 controls) did not observe any association between this SNP and the susceptibility to asthma [ 49 , 61 ].…”

“…These elements are essential parts of the immune system in its protective mission at pulmonary level [ 23 , 24 , 47 , 48 ]. Previous studies have discovered a genetic correlation between polymorphisms in the vitamin D metabolic pathway and asthma, due to the start of inflammatory processes and deregulation of the immune system, mainly in a pediatric population [ 6 , 7 , 49 , 50 , 51 ]. Our study was carried out in order to ascertain the influence of eight genetic polymorphisms located in the main genes that regulate vitamin D metabolism ( CYP24A1, GC, CYP27B1 and CYP2R1 ) and five SNPs in the gene that encodes its receptor ( VDR ) on the susceptibility to asthma, in a Caucasian population in southern Spain.…”

Vitamin D Receptor Gene Polymorphisms and Risk of Atopic Dermatitis in Chinese Han Population

“…Future studies should pay attention to allergic comorbidity. 38 Finally, although we found VDR gene variations affect the VDR mRNA expression, and the VDR gene polymorphisms may be associated with AD via regulating vitamin D level. This specific molecular mechanism needs to be further explored.…”

The Sun also rises

“…The complexity of the relationship between vitamin D and asthma is amplified by the importance of variants in many genes that affect the regulation of vitamin D, which include the genes along the metabolic pathway, together with the genes of receptors in epithelial and bronchial smooth muscle, which increase the expression of various cytokines and interleukins, as well as contributing to the association between vitamin D and inflammation. 6 …”

“…Although there are many reasons for the rise of controversies around vitamin D, much of the blame can be laid at the feet of Dr. Michael Holick. Together with the discrepant findings published in scientific journals, 3 - 6 the subject has occupied editorial spaces in the lay press. According to an article published in The New York Times on 08/18/2018, Dr. Holick’s enthusiasm for vitamin D surpassed the limits of good science practice and entered the nebulous terrain of conflicts of interest.…”