Emily Wasserman, Rika Gomi, Anurag Sharma, Seunghee Hong, Rohan Bareja, Jinghua Gu, Uthra Balaji, Arul Veerappan, Benjamin I Kim, Wenzhu Wu, Andrea Heras, Jose Perez-Zoghbi, Biin Sung, Seyni Gueye-Ndiaye, Tilla S Worgall, Stefan Worgall
The 17q21 asthma susceptibility locus includes asthma risk alleles associated with decreased sphingolipid synthesis, likely resulting from increased expression of ORMDL3. ORMDL3 inhibits serine-palmitoyl transferase (SPT), the rate-limiting enzyme of de novo sphingolipid synthesis. There is evidence that decreased sphingolipid synthesis is critical to asthma pathogenesis. Children with asthma and 17q21 asthma risk alleles display decreased sphingolipid synthesis in blood cells. Reduced SPT activity results in airway hyperreactivity, a hallmark feature of asthma...
March 2022: American Journal of Respiratory Cell and Molecular Biology