The Vitamin D Receptor Gene Polymorphisms in Asthmatic Children: A Case-Control Study

Abstract

Background: The association between vitamin D receptor (VDR) polymorphisms and the risk of asthma remains unclear. This study aimed to investigate the effect of VDR gene polymorphisms and VDR mRNA expression levels on respiratory function, nitric oxide levels in expiratory air, and serum vitamin D levels in children with asthma. Materials and Methods: The study included 80 healthy children (control group) and 100 asthmatic children (asthma group) between the age of 5 and 18 years. The VDR genotypes (ApaI, TaqI, and FokI) and VDR mRNA levels were determined in all groups. Results: There was no statistically significant difference in vitamin D levels between the asthma group and the control group (P > 0.05). A significant association was found between both genotype (CC) of the TaqI polymorphism [odds ratio (OR) = 0.2, 95% confidence interval (CI) (0.07-0.5), P = 0.003] and genotype (CA) of ApaI polymorphisms [OR = 0.2, 95% CI (0.07-0.8), P = 0.02], and asthma risk. In addition, when singlenucleotide polymorphism allelic frequencies between asthma and control groups were compared there is no significant association (P > 0.05). When compared to control group, VDR mRNA expression in asthma group decreased in genotypes CC and CA of ApaI and in genotypes TT and TC of TaqI (P < 0.05). Conclusion: The results provide supporting evidence for an association between TaqI and ApaI polymorphisms and asthma susceptibility.

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

“…As both had similar ethnic population the difference in age group of the population could be attributed as the reason for this variation. Interestingly study done by Wjst et al done in Germany [ 16 ] had found no association in family transmission [ 12 , 25 , 27 , 28 , 29 , 31 , 32 , 33 , 36 , 37 ] ( Figure 3 , Table 3 ).

Figure 3 Forest Plot analysis of Apa 1 polymorphism.

…”

“…Difference was noticed in the subgroup analysis with Asian asthmatic children showing significant association in homozygous major form (OR 0.68 (0.51,0.92) and African children with homozygous minor allele (OR 0.43 (0.23,0.80). Thus, it can be inferred that Taq 1 polymorphism had varying association depending on ethnicity with asthmatic children [ 15 , 25 , 28 , 29 , 31 , 32 , 33 , 36 , 37 ].…”

“…In contrast, the Egyptian population showed significant protective association of major allele in homozygous form with asthmatics (OR 0.28 (0.17,0.44). There was also significant association of minor allele in homozygous with OR 2.32 (1.40, 3.83) and in heterozygous form with OR 1.75 (1.14, 2.68) [ 12 , 25 , 29 , 30 , 31 , 32 , 33 , 34 , 37 ].…”

Asthma susceptible genes in children

“…The included studies were published between 2010 and 2020 and conducted in 11 countries: China, Indian, Egypt, Jordan, Poland, Mexico, Saudi Arabia, Colombia, Chile, Turkey, and Tunisia. A total of 18 polymorphisms in 7 genes were identified for data synthesis: IL-13 +2044G/A (rs20541), [ 10 – 15 ] IL-13 -1112C/T (rs1800925), [ 11 , 13 , 15 – 19 ] IL-13 +1923C/T (rs1295686), [ 20 – 22 ] IL-4 - 590C/T (rs2243250), [ 12 , 15 – 19 , 21 , 23 – 28 ] ADRB2 -46 G /A (rs1042713), [ 11 , 15 , 21 , 29 – 37 ] ADRB2 -79G/C (rs1042713), [ 29 , 31 – 35 , 38 ] ADAM33 F+1 (rs511898), [ 39 – 42 ] ADAM33 V4 (rs2787094), [ 39 , 40 , 43 – 45 ] ADAM33 S2 (rs528557), [ 15 , 39 , 41 , 44 , 45 ] ADAM33 T2 (rs2280090), [ 40 , 43 – 46 ] ADAM33 T1 (rs2280091), [ 40 , 41 , 44 , 45 ] ADAM33 ST+4 (rs44707), [ 39 , 47 , 48 ] ORMDL3 rs7216389, [ 49 – 52 ] VDR Apa I (rs7975232), [ 53 – 59 ] VDR Fok I (rs2228570), [ 53 – 55 , 57 , 58 , 60 , 61 ] VDR ...…”

Asthma susceptible genes in children: A meta-analysis

“…The included studies were published between 2010 and 2020 and were conducted in ten countries: China, Indian, Egypt, Jordan, Poland, Mexico, Saudi Arabia, Colombia, Turkey and Tunisia. A total of 18 polymorphisms in 7 genes were identi ed for data synthesis: IL-13 + 2044G/A (rs20541) 10-14 , IL-13 -1112C/T(rs1800925) 11,13,15−18 , IL-13 + 1923C/T (rs1295686) 19,20 , IL-4 -590C/T (rs2243250) 12,15-18,20−25 , ADRB2 -46 G /A(rs1042713) 11,20,26−31 , ADRB2 -79G/C (rs1042713) 26,28−32 , ADAM33 F + 1(rs511898) 33-36 , ADAM33 V4 (rs2787094) 33,34,37−39 , ADAM33 S2(rs528557) 33,35,38,39 , ADAM33 T2 (rs2280090) 34,37−39 , ADAM33 T1(rs2280091) 34,35,38,39 , ADAM33 ST + 4 (rs44707) 33,40,41 , ORMDL3 rs7216389 42-44 , VDR Apa (rs7975232) [45][46][47][48][49] , VDR Fok (rs2228570) 45-47,49−51 ,VDR Bsm (rs1544410) [46][47][48][49]51 , VDR Taq (rs731236) [45][46][47]49 , and CTLA-4 + 49 G/A (rs231775) [52][53][54] . The detailed characteristics of included studies are given in Table 1.…”