Are polymorphisms in LTC4 synthase associated with asthma phenotype?

Kedda et al (p 889) have used a large Australian Caucasian adult population of nonasthmatic individuals, individuals with mild/moderate/severe asthma, and aspirin-intolerant asthmatic individuals to look for associations between 2 polymorphisms in the LTC4 synthase gene and different asthma phenotypes. They have identified a new polymorphism (IVS1-10c>a), which was not associated with asthma or asthma severity, and they have conducted association studies of the A−444C polymorphism, previously shown to be associated with aspirin-intolerant asthma. In this population, they have shown that the A−444C polymorphism was weakly associated with asthma per se, but not with chronic asthma severity or aspirin intolerance. They also conducted a meta-analysis of all of the genetic association studies conducted to date and have shown significant between-study heterogeneity in C−444 allele frequencies within different clinical subgroups. In vitro studies revealed no significant functional differences between the A−444 and C−444 alleles. The authors have thus confirmed that independent of transcriptional activity, the C−444 allele in the LTC4 synthase gene is weakly associated with the asthma phenotype but is not related to disease severity or aspirin intolerance.