Lack Of Association Between ADAM33 Gene Polymorphisms And Asthma In A Huadong Chinese Han Population

Background:Asthma,a polygenic hereditary disease,is induced by both hereditary factor and environmental factors.Recently,hundreds of genes have been associated with asthma, and ADAM33 gene is one of the hot spots,it is associated with asthma and bronchial hyperresponsiveness.The SNPs of ADAM33 gene,however,differ in their associations with the development of asthma and the related phenotypes in populations.To date,association of polymorphisms in locus SI&S2 with the development of asthma and pulmonary function has not been studied in Chinese Han population.Objective:Unrelated asthmatics and healthy controls of Huadong Chinese Han population were included in this case-control study.To investigate whether polymorphisms of locus SI&S2 in ADAM33 gene are associated with asthma and pulmonary function, the genotype frequencies and allele frequencies of different groups were analyzed.Methods:The study included 147 unrelated asthma patients and 73 healthy controls. Peripheral venous blood samples were taken,and the genotypes of locus S1&S2 were tested.We followed up the asthmatics,that were taken graded treatment,till there's no further improvement of their pulmonary function,and the best FEV₁ results in this period were recorded.The asthmatics were classified into two groups: normal-pulmonary-function asthmatics(FEV₁ actual value/ predicted value≥80%) and decline-pulmonary-function asthmatics(FEV₁ actual value/ predicted value＜80%).And the asthmatics,whose FEV₁ actual value/ predicted value＜50%, were grouped into sever asthmatic group.The subjects were compared in three different ways:asthmatics/healthy controls,normal-pulmonary-function asthmatics/ decline-pulmonary-function asthmatics,sever asthmatics/ healthy controls.We compared the sex and age of various groups,and evaluated each variation for deviations from Hardy-Weinberg equilibrium.The genotype distributions and allelic frequencies for studied polymorphisms for the various groups were statistically compared.The linkage disequilibrium was measured between locus S1 and locus S2, and frequencies of haplotypes were compared between groups.FEV₁ of asthmatics with different genotypes were compared.The allelic frequencies of healthy controls were compared between populations.Results were considered statistically significant when the probability of findings occurring by chance was less than 5%(P＜0.05).Results:Sex and age of subjects in various groups were comparable.At locus S1,frequency of genotype A/G,G/G were 12.2%,87.7%,and frequency of allele A,G were 6.1%,93.9%in asthmatics,while frequency of genotype A/G,G/G were 8.2%,91.8%,and frequency of allele A,G were4.1%,95.9%in healthy controls. At locus S2,frequency of genotype C/C,C/G,G/G were 4.1%,33.3%,62.6%,and frequency of allele C,G were 20.7%,79.3%in asthmatics,while frequency of genotype C/C,C/G,G/G were 4.1%,35.6%,60.3%,and frequency of allele C,G were4.1%,95.9%in healthy controls.Frequency of genotype and allele were not statistically significant.At locus S1,frequency of genotype A/G,G/G were 8.9%,91.1%,and frequency of allele A,G were 4.4%,95.6%in normal-pulmonary-function asthmatics,while frequency of genotype A/G,G/G were 16.2%,83.8%,and frequency of allele A,G were8.1%,91.1%in decline-pulmonary-function asthmatics.At locus S2,frequency of genotype C/C,C/G,G/G were 3.8%,34.2%,62.0%,and frequency of allele C,G were 20.7%,79.3%in normal-pulmonary-function asthmatics,while frequency of genotype C/C,C/G,G/G were 4.1%,35.6%,60.3%,and frequency of allele C,G were 20.6%,79.4%in decline-pulmonary-function asthmatics.Frequency of genotype and allele were not statistically significant.At locus S1,frequency of genotype A/G,G/G were 8.3%,91.7%,and frequency of allele A,G were 4.1%,95.9%in sever asthmatics,while frequency of genotype A/G,G/G were 8.2%,91.8%,and frequency of allele A,G were 4.2%,95.8%in healthy controls.At locus S2,frequency of genotype C/G,G/G were 29.2%,70.8%, and frequency of allele C,G were 21.9%,78.1%in sever asthmatics,while frequency of genotype C/C,C/G,G/G were 4.1%,35.6%,60.3%,and frequency of allele C,G were4.1%,95.9%in healthy controls.Frequency of genotype and allele were not statistically significant.The measured LD was low between tested polymorphisms,and the frequencies of haplotypes were not statistically significant.At locus S1,FEV₁ actual value/predicted value of genotype A/G,G/G were 78.0±22.1%,77.4±22.7%.At locus S2,FEV₁ actual value/predicted value of genotype C/C,C/G,G/G were 78.7±23.5%,78.3±21.3%,77.0±23.3%.No significant difference was observed.At locus S1,compared to Huadong Chinese Han population,the allelic frequencies were statistically significant in UK Caucasian,US Caucasian,Dutch Caucasian,African American,US white and Germany,while the allelic frequencies were not statistically significant in US Hispanic,Mexican,Puerto Rican and Korean. At locus $2,compared to Huadong Chinese Han population,the allelic frequencies were statistically significant in African American,US white,Germany,while the allelic frequencies were not statistically significant in UK Caucasian,Dutch Caucasian,US Hispanic and JapaneseConclusion:The polymorphisms of locus S 1 &S2 showed no association with the development of asthma and pulmonary function in Huadong Chinese Han population.