Genetic markers for asthmatic Saudi population

Abstract

Background: Asthma is classified as a multifactorial disease with both genetic and environmental factors contributing to its development. Many studies have been carried out to determine the role of genetic susceptibility in the development of asthma. They found heritability risk for asthma is up to 60%. The number of genes contributing to asthma may exceed 100. Most of the genes found are associated with asthma inflammation process. Polymorphisms contributing to innate immune molecules were investigated for their association with asthma. Novel polymorphisms associated with asthma have been identified in multiple populations. Objectives: This study aimed to screen 5 common variants (IL13 Arg144Gln A>G rs20541, IL13 C1111T C>T rs1800925, IL4Rα Ile50Val A>G rs1805010, IL4Rα Gln551Arg A>G rs1801275 and MS4A2 Glu237Gly A>G rs569108) in 3 different genes (IL13, MS4A2 and IL4Rα) which specifically associate with asthma in both adult and pediatric subjects; to determine the common variants in the asthmatic Saudis and allele frequencies of each variant in both asthmatic and normal Saudi individuals and to compare frequency of alleles in the asthmatic Saudis with that in other populations; and, in addition, to identify genetic markers for asthma in the Saudi population. Materials and Methods: The study was approved by the ethics committee at the College of Medicine and King Khalid University Hospital (KKUH), King Saud University, Riyadh, Saudi Arabia. Informed consent was obtained from all study patients; or in case of children, from their guardians. Each subject completed a general questionnaire on respiratory health and family history of asthma. Blood samples were collected from 50 asthmatic adults and 50 asthmatic children attending clinics of the KKUH. The diagnosis was based on routine diagnostic parameters. As controls, blood was also collected from 50 normal, healthy adults attending the blood bank and 50 healthy children not suffering from asthma and attending the hospital for minor illnesses. DNA extraction and genotyping: DNA was extracted using the Illustra blood GenomicPrep Mini Spin kit from GE Healthcare Amersham, UK, according to the manufacturer's instructions. Subjects were genotyped for each polymorphism by direct PCR-sequencing method or real-time PCR for allelic discrimination. Results: Allele associations: We compared the genotype frequencies and allelic to all of the study single nucleotide polymorphisms (SNPs) among asthma patients with those among controls. P value was not significant for all variants except one SNP show association with asthmatic pediatric comparing to their control, although statistically not significant (0.0537). This SNP (rs1801275) in IL4R gene which was located in exon 11. This study polymorphisms Arg144Gln G>A and C1111T C>T effecting IL-13 plasma level in the presence of homozygous mutant allele. Therefore, finding this relationship need to be investigated that had been failed due to absence of the mutant allele but there was a significant difference between the two groups. Population analysis of study SNPs: Our data was compared with that of other populations. There was extreme difference in some populations, which was not the case in other populations. Conclusion: The lack of replication of this association study could be due to the different SNPs tested, to different ethnicity-specific effects of particular SNPs, or to the relatively small number of subjects analyzed in this study. This can be seen clearly with asthmatic pediatric population's result for IL4Rα variant.