Association Of ADAM33Gene Polymorphisms And Their Haplotypes With Asthma In The Guangxi Zhuang Population Of China

Objectives To evaluate the potential influence of T1, V4, T2and S2polymorphic sites in ADAM33gene on asthma in the Guangxi Zhuangpopulation of China.Methods A case-control study was conducted.226individuals were involvedincluding107asthma patients and119healthy controls. Genotypes weredetermined by the polymerase chain restriction fragment lengthpolymorphism (PCR-RFLP) method. Data were analyzed using SPSS16.0、SHEsis and STAT11.0softwares.Results1. The analytic results of single SNP associated with asthma(1) T1, V4, T2and S2polymorphisms in ADAM33gene were exist in theGuangxi Zhuang population of China. The distributions of these four SNPswere in Hardy–Weinberg equilibrium (p>0.05) in both groups of case andcontrol cohorts.(2) The distributions of T1and S2variants allele frequencies as well as S2variant genotype frequency were statistics different in case and control groupsthrough chi-square (χ2) test，whereas these associations were not found in the distributions of genotype frequency of T1variant, allele frequencies andgenotype frequencies of V4and T2variants.(3) For T1, significant association with asthma was found in allele model(OR=0.554,95%CI=0.323-0.951), heterozygous model (OR=0.527,95%CI=0.280-0.994) and dominant model (OR=0.513,95%CI=0.279-0.946),but not homozygous model and recessive model through logistic regressionanalysis. For S2, we found significant association with asthma in allele model(OR=0.423,95%CI=0.273-0.654), heterozygous model (OR=0.527,95%CI=0.302-0.920) and dominant model (OR=0.421,95%CI=0.244-0.724).No evidence of related association was found in all of the genetic models forV4and T2variants.(4) A meta-analysis (including the current research data) to evaluate therelationship between ADAM33polymorphisms and asthma risk in Chinesepopulation was conducted. Significant association was found in allelic model(OR=1.761,95%CI=1.159-2.676), heterozygous model (OR=1.216,95%CI=1.013-1.459) and dominant model (OR=1.932,95%CI=1.201-3.107)for T1variants, but not homozygous model and recessive model. For T2,significant association was found in all of the genetic models, the result wasas follows: in allelic model (OR=1.559,95%CI=1.068-2.274), homozygousmodel (OR=2.392,95%CI=1.067-5.363), heterozygous model (OR=1.534,95%CI=1.045-2.251), dominant model (OR=1.588,95%CI=1.065-2.369) andrecessive model (OR=2.291,95%CI=1.023-5.132). There was not significantassociation was found for V4and S2variants in all of the genetic models.2. Linkage disequilibrium and haplotype analysisStrong linkage disequilibrium ((D’>0.5) was found between the followtwo SNPs: T1and V4, T1and S2, T1and T2, S2and T2, whereas SNPs V4 and S2, V4and T2were not in linkage disequilibrium ((D’<0.5). Haplotypeanalysis was conducted in the four SNPs, and a total of five haplotype appearfrequencies were greater than0.03in both case and control groups. Thefrequency of the haplotype H2(ACGG) was different in case and controlgroups (χ2=6.904, P=0.009, OR=0.355,95%CI=0.160-0.791). Thedistribution of haplotype H3（AGCG）frequency in case and control groupswas also different(χ2=4.680, P=0.031, OR=1.540,95%CI=1.041-2.279). Nosignificant differences can be observing for haplotypes H1, H4, and H5between asthma and control groups.Conclusion(1) The polymorphisms of T1, V4, T2and S2variants in ADAM33gene wereexist in the Guangxi Zhuang population of China.(2) In Guangxi Zhuag population, the distributions of T1allele frequency aswell as S2variant allele frequency and genotype frequency were statisticsdifferent in case and control groups.(3)Logistic regression analysis also showed that T1(A→G) and S2(C→G)polymorphisms may reduce risk of asthma in the Guangxi Zhuang population,whereas V4、T2polymorphisms may not association with asthma.(4) In Guangxi Zhuag population, haplotype ACGG may reduce risk ofasthma, whereas haplotype AGCG may increase asthma risk.