Genotype polymorphisms in IL-4, IL-5 and IL-13 genes
The cause of allergic asthma is by environmental and genetic factors that interact to determine disease susceptibility and severity. Most lines of evidence suggest that the interleukin (IL-4 and the IL-4 receptor alpha (IL-4Raphla) are engaged in the spread of atopic diseases. A study was conducted in a population to determine whether polymorphism sites in IL-4 and IL-4 Ralpha chain are associated with allergic asthma. Clinical data and DNA from allergic asthma patients were obtained; they were compared with those of a group of healthy control subjects. The subjects were genotyped for the IL-4R alpha chain Q576R and the IL-4 C-590T promoter polymorphism by polymerase chain reaction-restriction fragment length polymorphism. Based on the results, it showed that the IL-4 C-590T was not related to allergic asthma in the population. Nonetheless, the IL-4R alpha chain 576R/R was notably increased in allergic asthma patients compared with control subjects (chi2 = 21.16; p<0.01), and the total plasma immunoglobulin E (lgE) level was raised in allergic asthma patients. The data implied that IL-4R alpha chain 576R/R genotypes confer susceptibility to allergic asthma.
IL-13 is a protein encoded by a gene that is a potent growth promoting cytokine. The cytokine is competent of supporting proliferation of a broad range of hematopoietic cell type. It is associated with a diversity of cell activities such as apoptosis, differentiation, and cell growth. The cytokine has also been shown to dominate neurotrophic activity, and it may be connected to neurologic disorders. Three previous genetic association studies carried out in China and Korea investigated between IL-13 single nucleotide polymorphism (SNP) rs40401 and asthma, but their results were inconstant. The focus was on the possibility and relationship between IL-13 rs40401 and smoking in young adult Japanese women. 89 women who met the criteria of the European Community Respiratory Health Survey (ECRHS) for asthma were included. The control subjects were 700 women who had no asthma or who had not been allergic to a doctor or diagnosed with asthma or who had not met the criteria of International Study of Asthma and Allergies in Childhood for rhinoconjunctivitis, this wa according to the ECRHS criteria. A remarkable positive association was found between SNP rs40401 and the risk of asthma, with the TT genotype as the reference under the additive model: the odds ratio adjusted was 1.39 (95% Cl: 1.004-1.93). The study suggests that IL-13 rs40401 is associated with the risk of asthma in young adult Japanese women and reveals that composition of ever smoking and having the CC genotype of IL-13 SNP rs40401 is significantly linked to asthma.
Kouriba, B., Chevillard, C., Bream, J. H., Argiro, L., Dessein, H., Arnaud, V. and Traore, (2005) reports that the study conducted in Korea to determine if IL-5 and IL-5 receptor alpha polymorphisms are associated with atopic dermatitis (AD) Singlenucleotide polymorphisms (SNPs) (17) were genotyped from five genes of the 1120 case-control samples (447 controls and 646 AD). Serum IL-5 concentrations in 87 individuals [36 ADe(AD extrinsic), 18 ADi(AD intrinsic) and 33 controls] were measured and results compared among the groups. From the results, haplotype T-A in the IL-5 gene and the rs25224111SNP were significantly associated with the Ade. The concentration of serum IL-5 was higher in the ADe than that in ADi patients without any correlation with the rs25224111SNP. In the IL-5RA gene, the rs334809SNP showed a weak association with AD, and the rs6771148SNP and the haplotype T-C-T of the three adjacent tagged SNPs had an effect on the blood eosinophil counts and the serum ECP levels in the AD patients. In conclusion, it was found that the rs25224111SNP and the haplotype T-A in the IL-5 gene and the serum IL-5 levels were strongly associated with the allergic type of AD, but with the non-allergic type of AD. Steinmann , Keiser, Bos , Tanner and Utzinger (2006)implies that the association of the rs6771148SNP and the haplotype T-C-T in the IL5RA gene with the blood eosinophil counts and the serum ECP levels indicates that the IL5RA gene has a role in controlling eosinophils in the peripheral blood
Relationship between Schistosome infections and polymorphisms
Genetic research of human susceptibility to Schistosoma (blood fluke) infections have previously identified a genetic locus was determining the intensity of infection with African species, Schistosoma mansori. The human genome in the region 5q31-33 which is known to contain the Th2 immune response cluster, including the genes encoding the IL-4, IL-5, IL-10 and IL-13 cytokines. These cytokines play a vital role in inflammatory immune response, and they have been previously incriminated in human susceptibility to infection with the Asian species, S. japonicum. A nested case control study conducted, 30 HipMap tagging single nucleotide polymorphism (SNP) were genotyped across the four genes in 133 individuals identified as putatively resistant and 159 individuals identified as putatively susceptible to reinfection with S. japonicum. A third group composed of 113 individuals was included to demonstrate symptomatic infection. The final results no significant association a global level between haplotype blocks or any of the individual SNPs. However, two tagging SNPs in IL-5 elaborated globally significant association with susceptibility to symptomatic infection. There was a strong relation imbalance with each other and others were found to belong to the same haplotype block that also provided valuable association after permutation testing. The location of ha plotype was in the 3-untranslated region of IL-5, implying that variant in this region IL-5 may modulate the immune response in these individuals with symptomatic infection.
Henri, S., Chevillard, C., Mergani, A., Paris, P., Gaudart, J., Camilla, C. Magzoub and M. (2002) report that millions of people are exposed to schistosome infection that causes severe liver and kidney disease and a total death of 280,000 annually. The genetic locus IL-5, IL-4, and IL-13 control the Th2-mediated immunity that is critical to human defenses against this susceptibility to infection and pathogen. These observations begged the need for evaluating whether particular polymorphism in IL-4, IL-5 and IL-13 controlled schistosome infection. The study was carried out in two areas where schistosome haematobium is endemic. Schistosome infections were assessed by measuring worm ages in urine and counting eggs. Restriction enzyme analysis or primer extension and denaturing high-performance liquid chromatography analysis were used to determine genetic polymorphism. Associations were also tested using logistical regression analysis and family-based relationships test. The alleles IL13-591A (p = 0.01) and IL13-1055C (p = 0.05) are shown, by family based-association test, specially transmitted to children with the 10% highest infections. A logistic regression analysis that encompasses IL13-1055 G/G, G/T and T/T genotypes, gender, village, age and residency, applied to the entire population of study, revealed that subjects bearing the IL13-1055 genotype were averagely much less infected than individuals with other genotypes. Antecedent studies on asthma showed that the IL13-1055 allele increased the transcription of genes, which is by the fact that this cytokine intensifies resistance to infection by schistosome in humans.
