Single nucleotide polymorphisms in asthma candidate genes TBXA2R , ADAM33 FCER1B and ORMDL3 in Pakistani asthmatics a case control study.

Background: Genetic variations in different loci and genes are important in asthma pathogenesis. There is much importance of various immunological pathways in the IgE secretion regulation. Alterations in any main part of these pathways can increase the risk of asthma development. Polymorphisms in these genetic markers can effect certain pathways which predict the asthma susceptibility. In the present study, SNPs directly or indirectly affecting the immunological process pathways are selected.

Methods: This study was conducted to determine association of 16 SNPs in 10 candidate genes with asthma in Pakistani population in 333 asthmatic cases and 220 healthy controls. Genotyping was performed using the Sequenom Mass ARRAY iPLEX platform (14 SNPs) and TaqMan assay (2 SNPs).

Results: The minor allele at two of the SNPs showed association with protection from asthma, rs1131882 in TBXA2R gene (OR 0.73, 95% CI 0.52-1.01, P  = 0.05) and rs2280091 in the ADAM33 gene (OR 0.69, 95% CI 0.50-0.97, P  = 0.03). For FCER1B gene, rs2583476 the asthmatic male gender had higher TT genotype counts as compared to controls (OR = 1.86, 95% CI = 1.09-3.17, p  = 0.01). In rs11650680 of ORMDL3 gene the CT genotype is more prevalent in female asthma cases in comparison with female controls (OR = 1.99, 95% CI = 1.02-3.89, p  = 0.03).

Conclusions: This data suggests that variations at TBXA2R and ADAM33 genes are found to be associated with asthma susceptibility in Pakistan. FCER1B gene is associated with male and ORMDL3 in female asthmatics. These genetic markers can be important source of asthma risk in Pakistani population.