Association Study Of Asthma And Polymorphism In IL7R Gene In A Chinese Han Population

Background:Asthma is a chronic inflammatory pulmonary disorder which attacks repeatedly. As a complex disease, the development of asthma is determined by the interaction of genetic and environmental factors. The number of susceptibility genes associated with asthma has increased quickly in the past several years. In this study we present the study of the association of candidate gene interleukin seven receptor IL7R with asthma. IL7R was selected based on its chromosomal location (chromosome 5) and biological function in asthma and other autoimmune disease such as Severe Combined Immunodeficiency (SCID) and Multiple Sclerosis (MS). It is located in a chromosomal region that is rich in genes coding for key molecules like cytokine and growth factors. IL7R plays an important role in the maturation and the survival of T cell in human. Its ligand IL7 is expressed in epithelial cells in many tissues and has different biological effects. Also, a foreign group has mapped an asthma susceptibility locus to 5p13 which contains IL7R gene. So in this study we used the single nucleotide polymorphism (SNP) as genetic markers to test the possible association between interleukin seven receptor and asthma in Chinese Han population. Objective:The main objective of this study was to study the association between asthma and IL7R gene in a Chinese Han population. Three polymorphisms located in exon 2 (rs1494558) and promoter (rs11567686), intron 3(rs10063445) were selected and genotyped.Materials and Methods:The samples in this study were collected from Shandong Province and all are Han Chinese. The total number of the subjects is 824, including 400 controls and 424 patients. All the three SNPs were genotyped using PCR-RFLP and restriction endonuclease BstxI was used for rsl494558, HphI for rsl 1567686, Taq I for rsl0063445. The genotypes of the polymorphism sites were determined according to the electrophoresis results. The genotype and allele frequencies of different polymorphisms were calculated in both asthma patients and healthy controls.Each polymorphism was evaluated for Hardy-Weinberg Equilibrium (HWE) using chi-square test. Only polymorphisms that follow Hardy-Weinberg equilibrium in both asthma patients and healthy controls were used in the study. The distribution of different genotypes and alleles of every polymorphism in the two groups was compared using chi-square test to determine whether the polymorphism is associated with asthma.SHEsis software was used to determine whether the three SNPs are in linkage disequilibrium. If polymorphisms in the same gene are in linkage disequilibrium, haplotypes were constructed and the haplotype distributions in the two groups are compared. Results:All the three SNPs are in agreement to HWE. For rs11567686, its genotypes and alleles distribution are not statistically different between asthma patients and healthy controls. (all P>0.05). For rs1494558 and rs10063445, both the genotype and allele frequency distribution of the two SNPs are statistically different between asthma patients and healthy controls. (P=0.040; P=0.031). Moreover, high LD was detected between the rs1494558 and rs11567686 with D'=0.569.Conclusion:Our results suggest that IL7R gene is associated with asthma in Chinese Han population, and maybe a susceptible gene of asthma, but these results need to be replicated in other populations.