Linkage to atopy on chromosome 19 in north-eastern Italian families with allergic asthma

Background Allergic asthma is a multifactorial disease for which there is a widely assessed, although poorly understood, genetic involvement. Genome-w ide screens reported evidence for linkage of allergic asthma-related phenot ypes to several chromosomal locations. Markers on chromosome. 19 have been linked to allergic asthma phenotypes in different populations in independen t studies. Objective The aim of this study was to perform a genetic linkage analysis o n chromosome 19 to search for DNA markers linked to phenotypes related to a llergic asthma. Methods Using non-parametric multipoint linkage analysis on a total of 22 r andom DNA markers in 2 stages, a sample of 111 families (542 subjects) from north-eastern Italy, recruited through an asthmatic allergic proband, was investigated. Phenotypes examined were: clinical asthma, total serum elevat ed IgE, skin prick test positivity, bronchial hyperresponsiveness, and atop y defined as skin prick test positivity and/or elevated IgE. Simulation stu dies were performed to confirm the significance of the results. Results A novel linkage of atopy and skin prick test positivity to marker D 19S601 (19q13.3) was found. Modest evidence for linkage of atopy, skin pric k test positivity, and IgE was also found to marker D19S591 (19p13.3). Simu lation analysis for atopy gave an NPL-Z > 3.326 in 2 replicates out of 1000 (P = 0.002) for D19S601, and an NPL-Z > 2.56 in 16 replicates out of 1000 (P = 0.016) for D19S591. Conclusions On chromosome 19, suggestive linkage of atopy and skin prick te st positivity with marker D19S601 (19q13.3) and modest evidence of linkage of marker D19S591 (19p13.3) to the atopic phenotypes investigated were foun d. These results suggest that these regions may contain susceptibility loci associated to atopic phenotypes.