Association and Linkage of Atopic Dermatitis with Chromosome 13q12–14 and 5q31–33 Markers (original) (raw)
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Linkage and association to candidate regions in Swedish atopic dermatitis families
Human Genetics, 2001
We have studied, in 406 families with at least two siblings affected with atopic dermatitis (in total 1514 individuals) from the Swedish population, linkage and association to five chromosomal regions (2q35, 5q31-33, 6p21, 11q13 and 14q11) previously implicated in atopic diseases. The region on 14q11 gave evidence for linkage to atopic dermatitis (NPL-score: 2.36, P<0.009). In the 11q13 region, there was a clear association to an intragenic marker in the β-subunit of the high-affinity IgE receptor for raised allergen-specific serum IgE levels (P<0.009). When a quantitative variable for the severity of atopic dermatitis was studied, evidence was found in favour of linkage to the 5q31-33 region, with the highest Z-score (2.06) close to the marker D5S458 (P<0.005).
Allergy, 2005
Background: Dissecting complex diseases in underlying distinct traits and studying these for their genetic basis might enhance the power as well as the specificity, of detection of disease genes. These phenoypes are known as intermediate phenotypes.Objective: We were interested in the atopic basis of asthma, and used the sensitization to mite (Dermatophagoides pteronyssinus) allergens as a pathophysiologically important intermediate phenotype.Methods: This time we performed a genome-wide scan based on the same already used multiethnic European population consisting of 82 nuclear families with at least two affected siblings. We carried out nonparametric as well as parametric MOD-score analyses based on the genotypes of 603 microsatellite markers.Results: In comparison with our first genome-wide candidate region search three novel regions additionally appeared to be significant. We obtained significant results for the region 2p12 with a MOD score of 3.35 and for the region 16q21 with a MOD score of 4.18. The most significant result was found for the region 3q21.3 with the same microsatellite marker, which showed significant linkage to atopic dermatitis (AD) in another study with a MOD score of 4.51 and an nonparametric linkage analysis (NPL) of 4.00.Conclusion: Our findings indicate that atopy, allergic asthma, allergic rhinitis and AD on the one hand are distinct traits on both the clinical and genetic basis, but on the other hand, our results also underline that these traits are closely related diseases concerning the atopic basis of the traits.
Genetic analysis of the linkage between chromosome 11q and atopy
Clinical <html_ent glyph="@amp;" ascii="&"/> Experimental Allergy, 1992
Previous work has suggested that there is a genetic predisposition for the development of both asthma and atopy. A recent study has also shown that there is a striking link between chromosome llq and the IgE response underlying asthma and rhinitis. To further assess the linkage between chromosome 1 Iq and atopy, we have studied nine families of two and, in many instances, three generations with the index case having asthma and/or atopy. Using two restriction fragment length polymorphism probes associated with the regions Ilql2-ql3-2, namely PYGM and INT2. we have been unable to confirm a significant link between this region ofchromosome I Iq and atopy as defined by a positive skin-prick test and or a raised specific IgE and or a raised total IgF
Genome-wide search for atopy susceptibility genes in Dutch families with asthma
Journal of Allergy and Clinical Immunology, 2002
Background: Atopy is a phenotype associated with asthma that has a heritable component. However, the role of atopysusceptibility genes in the development and expression of asthma and allergic disorders is not understood. Objective: We sought to study the familial aggregation and cooccurrence of atopic phenotypes within family members of patients with asthma and to identify chromosomal regions that may contain genes that regulate different atopic phenotypes. Methods: In 200 families (n = 1174) ascertained through a proband with asthma, genome-wide screen and linkage analysis was performed for the following atopic phenotypes: (1) specific IgE to common aeroallergens (Phadiatop assay); (2) specific IgE to Der p 1; (3) positive skin test responses to house dust mite; (4) positive skin test responses to 1 or more of 16 allergens; and (5) peripheral blood eosinophils. Results were compared with the linkage results for total serum IgE levels. Results: There was clear familial aggregation of atopy. A high total serum IgE level in combination with a positive Phadiatop result or a normal total IgE level in combination with a negative Phadiatop result was found in 56.1% of the probands and 66.9% of the offspring. Several chromosomal regions that showed evidence for linkage to an atopic phenotype (ie, 2q, 6p, 7q, and 13q) also showed evidence of linkage with total serum IgE (Xu et al. Am J Hum Genet 2000;67:1163-73). Specific regions of interest for atopic traits were also detected on chromosomes 11q, 17q, and 22q. Conclusions: Atopic phenotypes show familial aggregation, although family members may differ in expression of atopy. Specific chromosomal regions appear to be important in susceptibility to different phenotypes of atopic responsiveness. (J Allergy Clin Immunol 2002;109:498-506.)
Characterization by phenotype of families with atopic dermatitis
Acta Dermato-Venereologica
The aetiology of atopic dermatitis is unknown, but is probably multifactorial, with interactions between several genetic and environmental factors. Twin studies indicate a strong genetic factor, but the susceptibility genes are unknown. This paper, describing the phenotypes of family material, forms part of a large genetic study seeking to identify susceptibility genes for atopic dermatitis by linkage analysis. We selected families with at least 2 siblings affected with atopic dermatitis (1,097 affected siblings who together form 650 affected sib pairs and 49 affected half-sib pairs). We established a phenotype database of information about the affected siblings and their relatives, in total 5,830 individuals. All siblings were diagnosed with atopic dermatitis and participated in a standardized interview covering aspects of atopy and atopic dermatitis. Of the affected siblings, 72% suffered or had suffered from asthma and/or allergic rhinoconjunctivitis and 74% had raised total and/...
Linkage to atopy on chromosome 19 in north-eastern Italian families with allergic asthma
Clinical <html_ent glyph="@amp;" ascii="&"/> Experimental Allergy, 2001
Background Allergic asthma is a multifactorial disease for which there is a widely assessed, although poorly understood, genetic involvement. Genome-wide screens reported evidence for linkage of allergic asthma-related phenotypes to several chromosomal locations. Markers on chromosome 19 have been linked to allergic asthma phenotypes in different populations in independent studies. Objective The aim of this study was to perform a genetic linkage analysis on chromosome 19 to search for DNA markers linked to phenotypes related to allergic asthma. Methods Using non-parametric multipoint linkage analysis on a total of 22 random 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 elevated IgE, skin prick test positivity, bronchial hyperresponsiveness, and atopy defined as skin prick test positivity and/or elevated IgE. Simulation studies were performed to confirm the significance of the results. Results A novel linkage of atopy and skin prick test positivity to marker D19S601 (19q13.3) was found. Modest evidence for linkage of atopy, skin prick test positivity, and IgE was also found to marker D19S591 (19p13.3). Simulation 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 test positivity with marker D19S601 (19q13.3) and modest evidence of linkage of marker D19S591 (19p13.3) to the atopic phenotypes investigated were found. These results suggest that these regions may contain susceptibility loci associated to atopic phenotypes.