Background: The ADAM family is involved in some pathologic processes, such as inflammation and asthma. Objectives: To assess the association between ADAM33 and ADAM12 single-nucleotide polymorphisms (SNPs) with asthma risk and severity and to investigate the effect of ADAM33 and ADAM12 polymorphisms on expression of these proteases in sputum. Methods: Two SNPs of the ADAM33 gene, Fþ1 (rs511898) G/A and STþ4 (rs44707) A/C, and 2 SNPs of the ADAM12 gene, rs3740199 and rs1871054, were analyzed in 400 asthma cases and 200 controls aged 3 to 14 years using the polymerase chain reactionerestriction fragment length polymorphism method. Messenger RNA expression profile of ADAM33 and ADAM12 proteases in sputum from studied groups was determined by reverse transcription polymerase chain reaction. Results: ADAM33 Fþ1 homozygous mutant genotype (AA) and STþ4 heterozygous and homozygous mutant genotype (AC and CC) and mutant alleles of both polymorphisms were significantly associated with asthma risk and severity in moderate and severe subgroups. Patients with the ADAM12 (rs3740199) CC genotype were at increased risk for moderate and severe asthma. Messenger RNA levels of ADAM12 were significantly increased in asthmatic children compared with controls, whereas we were not able to detect the expression of ADAM33 in the sputum of the groups studied. The ADAM12 expression was significantly higher in homozygous CC (variant type) compared with homozygous GG (wild type) of both ADAM12 rs3740199 and rs1871054 in the asthmatic group. Conclusion: Our analysis suggests a likely role for ADAM33 and ADAM12 in the development of asthma in Egyptian children