Asthma is an inflammatory chronic disorder of airways of lungs. In world, asthma is recognized as one of the most chronic diseases, which affects above 300 million people all round the world. In Pakistan, approximately 5-8% of adults are suffering from asthma. Both environmental and genetic factors contribute towards the development of disease. It is a multigenic disorder, and is due to different genetic factors, which also determine immune responses. The purpose of the present study is to identify and investigate polymorphisms in major asthma genes. In present study, 34 SNPs of 28 genes were genotyped by iPLEX and Taqman assay. HLA class II association was done by sequence specific PCR. It is found that the minor alleles of IL10 (rs1800896) and IL13 (rs1800925) are related to increased asthma risk in our population. It is also seen that the minor alleles of ADAM33 (rs2280091) are showing significant association with protection in Pakistani asthmatic population. ADAM33 minor allele is having protective effect in females. ACE homozygous insertion is reported to be associated with asthma risk in Pakistani population. HLA class II DRB1*07 and DQB1*03 are found to be important in asthma pathogenesis and DQB1*06 is showing statistically significant association with protection against the disease.