Published ahead of print on February 12, 2004, doi:10.1164/rccm.200302-228OC Am. J. Respir. Crit. Care Med., Volume 169, Number 9, May 2004, 1007-1013 A more recent version of this article appeared on May 1, 2004
Submitted on April 3, 2003 Genetic Approaches to Assessing Evidence for Th1-type Cytokine Defect in Adult AsthmaIllugi F Birkisson1,1 Medical Department, The University of Iceland, Reykjavik, Iceland, 2 Respiratory Division, deCODE Genetics Inc., Reykjavik, Iceland * To whom correspondence should be addressed. E-mail: hakonh{at}decode.is.
Recent evidence suggests that deficiency in the Th1 cytokine pathway may underlie the susceptibility to allergic asthma. This study examined whether: i) single nucleotide polymorphisms (SNPs) exist in the promoter region of the two IL-12 subunit genes in asthma patients, ii) mRNA and protein expressions of STAT4, IL-12, IFN- Key words: Asthma genetics; Genetic polymorphisms; Linkages
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, and their receptors are altered in asthma, and; iii) linkage to genes in the Th1 pathway is present in asthma families in Iceland. The promoter regions of the IL-12 subunit genes were sequenced in 94 asthmatic patients and 94 non-asthmatic controls. Linkage was examined in 169 families that included over 570 asthmatic patients and 950 of their unaffected relatives. The results demonstrate no evidence of linkage to microsatellite markers in close association with genes within the Th1 pathway, and no polymorphism was detected in the promoter regions of the two IL-12 subunit genes in the asthma patient cohort. Moreover, we found no differences in the mRNA or protein expression signals of genes in the IL-12 pathway between the patients and controls. We conclude that decrease in Th1 type cytokine response is unlikely to present a primary event in asthma.
