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Genetic Susceptibility to Asthma and Genetic Interactions in the 5q31-q33 and 16p11 Regions in Sudanese Families

Amal Osman, Mutaz Amin, Hiba Salah, Omer Abdelaziz and Muntasir Ibrahim

Background: Asthma is a complex disorder with heterogeneous phenotypes attributed to the interactions of many genes and the environment. Numerous genetic studies have mapped asthma susceptibility genes to a region on chromosome 5q31-q33. This study aimed to determine the association of 10 candidate polymorphisms in IL-4, IL-5, IL-9, IL-13 and IL-4R genes in 5q31-q33 region with susceptibility to asthma in Sudanese families.
Method: Fifty two multi cases families consisting of 141 known cases of asthma and 129 healthy individuals from Khartoum state were genotyped for seven SNPs on 5q31-33 region located in four candidate genes; IL4, IL5 IL13, IL9 and three SNPs in IL4Rα on chromosome 16p using multiplex PCR with Mass ARRAY system. Multiple logistic regression was used to test for association of asthma. P-value needed to achieve statistical significance taking multiple testing into account is P=0.005 (=0.05/10 (number of SNPs genotyped)). However, since SNPs within genes showed some degree of linkage disequilibrium and SNPs were selected as major SNPs for association with Asthma in other populations. Therefore, P £ 0.01 (=0.05/5 genes) can used as the P-value required to achieve correction for multiple testing.
Result: Genotype and allelic frequencies of all SNPs were similar in both asthmatics and healthy subjects. Stepwise logistic regression demonstrated that SNP IL-13 rs2069743 was markedly associated with Asthma (P=0.008) and same SNP added significant main effects to IL-4 rs2070874 or IL-9 rs31563, whereas the reverse was not true, indicating that the main effect for association with asthma in this population is most strongly tagged by SNP IL-13 rs2069743.
Conclusion: There is strong genetic association of SNPs in 5q31-q33 and 16p11 region and asthma.