Associations of genetic variants in ADAM33 and TGF-β1 genes with childhood asthma risk

Abstract

Abstract. The aim of the present study was to explore the associations of genetic variants in the ADAM33 and TGF-β1 genes with the risk of childhood asthma. A total of 299 asthmatic children and 311 healthy controls were recruited in the hospital-based case-control study. The asthmatic subjects were further divided into mild and severe groups according to disease severity. Single-nucleotide polymorphisms (SNP) at ADAM33 V4, T2, S2 and T1, and TGF-β1 C-509T and T869C were selected and detected with PCR-RFLP. The associations of the SNPs with asthma risk and severity were analyzed. The associations between the haplotypes of ADAM33 and TGF-β1 were also evaluated. Compared with the GG genotype, the GC and CC genotypes at V4 were associated with an increased asthma risk in children and the ORs were 2.92 and 10.56, respectively. Compared with the CC genotype, the CT/TT genotype at C-509T was associated with an increased asthma risk and the OR was 2.26. Subsequent to stratification by asthma severity, compared with the V4 GG genotype, it was found that the CG and CC genotypes were associated with a mild asthma risk and the ORs were 3.00 and 5.99, respectively. The SNP at C-509T (CT/TT vs. CC) was associated with mild asthma (OR=2.34), whereas a marginally significant association was detected between the SNP (CT/ TT vs. CC) and severe asthma risk (OR=2.19). The haplotype analysis revealed that, compared with the GGCA haplotype of ADAM33, significant associations of the haplotypes of CGCG, CGGA, GACA, GACG and GAGA with asthma risk were observed, and the ORs were 31.12, 12.24, 4.73, 30.85 and 4.83, respectively. No significant association was detected between the TGF-β1 haplotypes and asthma risk. The genetic variants at V4 and C-509T had the potential to modify the childhood asthma risk and the associations showed no notable difference with the disease severity. Thus, ADAM33 haplotypes provided more useful information in the prediction of asthma risk.

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 ...…”

Single Nucleotide Polymorphisms of Transforming Growth Factor-Β1 Gene as Potential Asthma Susceptible Variants in Punjabi Population of Pakistan

“…32 rs1800469 is a functional genetic variant of TGF-β1 that has been studied as a potent asthma susceptible variant in many populations. 23,24,33,34 rs2241715 is located in the intronic region of TGF-β1 that has been evaluated as a potential risk factor for asthma in various populations. 21,25,22 Current study is the first effort to evaluate the association pattern of these SNPs with asthma in Pakistani population.…”

“…24,33 In contrast to our findings, some studies have shown the significant association of SNP rs1800469 with asthma. 23,34 These dissimilarities in results might be owing to various factors like ethnicity, geographical locations, life style and environmental factors. Sample size is another important factor that can affect the outcome of case-control based population studies.…”

“…21,22 Similarly different strategies have been adopted to find association of SNPs rs1800469 and rs2241715 with asthma among different ethnic populations and the results showed amazing variations of marginal, strong and no association of these SNPs with asthma. [23][24][25][26] The contradictory results of previous studies suggest the need of screening of other populations for these variants to understand the molecular mechanism of the disease in a better way. 27,28 The objective of the current study is to investigate any association of polymorphisms rs1800469 and rs2241715 in TGF-β1 with asthma in Pakistani population.…”

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.…”