Association Between GPRA And MTHFR Gene Polymorphism And Bronchial Asthma In Children

Bronchial asthma( or asthma) is a chronic inflammatory disorder of theairways which involves many cells and mediators released from mast cells.Thischronic inflammatory disorder causes bronchial hyperresponsiveness andairflow into and out of the lungs to be restricted with recurrent attacks ofwheezing, shortness of breath, chest tightness, and coughing, which alwaysattacks and intensifies at night or in the morning, but most of the patients canrelieve by himself or drugs. Asthma is characterized by intermittent attacks ofwheezing dyspnea of exhalation or recurrent chest tightness and cough.People around the globe suffer from asthma and this number is risingduring recent decades. The latest investigation about asthma shows there are anestimated 150 million asthmatics world-wide and deaths from this conditionhave reached over 180,000 annually.Estimates indicate a worldwide prevalencerate of asthma is between 0.11%and 0.32% and increase at the rate of 1%annually. World-wide, the economic costs associated with asthma areestimated to exceed those of TB and HIV/AIDS combined. Its chronicrecurrent attacks have caused great damage to asthmatic subjects and theirfamilies physically and mentally, economy and society. According to the roughestimates, the number of asthmatics in China is about 30 million including 10million children.Among asthmatic children, 1/3 to 1/2 can prolong to adult,which indicates that prevalences of many adult asthmatics start in theirchildhood. The epidemiological investigations on the children of cities all overthe country in 1990 and 2000 also show the same trend. The numbers ofasthmatic children are 0.91% and 1.54% of the children population in citiesseparately,and has leapt by over 60% in ten years. The prevalence situation ofchronic respiratory system disease is also severe. Because the characteristics ofasthma are recurrent attacks and often severe attacks which can induce deathwithout medical care timely, in addition, this chronic condition will affectnormal studies, works and life of asthmatic subjects severely and brings heavyeconomic burden to families and society. Asthma has became a severe publichealth problem. Therefore, understanding the pathogenesis of asthma has animportant meaning to prevention and therapy of asthma. Asthma is a dieasecaused by the interaction between environment and heredity, which belong topolygenic hereditary disease or human complex disease. The studies of humangenome systemic scan confirm that there are the asthma-related genes indifferent regions of chromosome 1p, 2q, 3q24, 5q21-33, 6q21-33, 7p, 7q11-14,11q13,12, 14-24 ,13q21-24,14q11-13,16q11-12,17p12-17,19q13 and 20p13.Our study was designed to search for the susceptibility genes for asthmain children by screening two single gene polymorphisms (SNPs) of Gprotein-coupled receptor gene related asthma (GPRA) in human chromosome 7and a SNP of Methylenetetrahydrofolate reductase gene (MTHFR) in 1p36.3.We used children of Han nationality in North China as subjects. Polymerasechain reaction and restriction fragment length polymorphism (PCR–RFLP)were adopted to examine individual genotype. Statistical software SPSS andEXCEL were used to handle the data on genotype. Goodness of fit χ2 test wasused to detect whether SNPs distributions in the sample population were inHardy-Weinberg equilibrium. Then we determined whether GPRA gene andMTHFR gene were associated with bronchial asthma.Our study has screened three SNPs ,which as follows: rs324396, rs324374of GPRA gene and C677T of MTHFR gene. We have examined 118 asthmaticchildren diagnosed by the First Clinical Hospital of JiLin University throughmany clinical examinations including history , biochemical indicator andrespiratory functions etc) and 134 healthy control children who were examinedin the local Centers for Diseases Control and Prevention(CDC) at the same year.Goodness of fit χ2 test showed that the distributions of the genotypes for threeSNPs were all in Hardy-Weinberg equilibrium. The analysis between each SNPand bronchial asthma in children showed that allele frequency and genotypefrequency of C and T on rs324396 locus of GPRA were associated withbronchial asthma in children, the point mutation of T allele increased themorbid risk of bronchial asthma. Allele frequency and genotype frequency of Cand T on rs324374 locus of GPRA were not associated with bronchial asthma.The frequency distribution of allele C and T of cDNA 677 T allele of MTHFRwere associated with bronchial asthma, the point mutation of T allele increasedthe morbid risk of bronchial asthma in children.The findings of this study suggested that GPRA gene and MTHFR genemight be associated with bronchial asthma in children. However, theirmechanism still needs further study.