An asthma-associated genetic variant of STAT6 predicts low burden of ascaris worm infestation

Th-2 immune mechanisms are involved in the pathology of asthma and in the protective immune response to parasitic worms. Common upregulating genetic variants of Th-2 immune signalling are risk factors for asthma, and we tested whether they may confer a counteradvantage in protecting against parasitic worms. We examined the intensity of infection by the parasitic worm, Ascaris lumbricoides, by microsopic counting of ascaris eggs in the stool of 614 schoolchildren from an area of endemic ascaris infection in China. We investigated the relationship between the intensity of ascaris infection and common, asthma-associated genetic variants of Th-2 and Th-1 immune signalling. Ascaris egg counts per gram of stool (epg), mean 1068 epg, ranged from barely detectable (<240 epg) to heavy (similar to 9600 epg) in a skewed distribution. Logistic regression, after exploratory discriminant analysis, showed a major association between a common genetic variant of the 3'-UTR regulatory elements of the signal transducer and transactivating factor (STAT6) (P=0.0002) and egg counts, at the 77th centile. Linear regression after log transformation of egg counts confirmed a highly significant association with this STAT6 variant (P=0.001). Thus, a common, asthma-associated, genetic variant of the pivotal transduction and transactivating factor for Th-2 immune signalling, STAT6, predicts increased resistance to ascaris worm infection. The evolution of enhanced resistance to parasitic worm infection, through human genetic variation in Th-2 immune signalling, may represent one origin for asthma.