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  • 1
    Electronic Resource
    Electronic Resource
    Association scan of the novel psoriasis susceptibility region on chromosome 19: evidence for both susceptible and protective loci (2003)
    Oxford, UK : Munksgaard International Publishers
    Experimental dermatology 12 (2003), S. 0 
    Details
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  To follow up the novel psoriasis susceptibility region on chromosome 19 (PSORS6), we performed an association scan for psoriasis vulgaris using 45 evenly spaced DNA microsatellite markers. For this study, a new independent sample of 210 nuclear psoriasis families (trio design) from Northern Germany was recruited. We used the family based association test (FBAT) for an association scan over the chromosome 19 region encompassing 50.8 cM. We obtained a positive association for the markers D19S922 (allele 5, P = 0.008) and D19S916 (allele 13, P = 0.016), which correspond to the peak of the region identified in a previously performed scan. We identified two novel regions by a single marker, each showing negative association at D19S917 on 19p13.1 (allele 8, P = 0.0034) and at D19S425 (allele 9, P = 0.0005), compatible with the hypothesis of protective loci. These two novel regions were explored in more detail using novel microsatellite markers at an average distance of 100 kb. A separate analysis distinguishing between familial (n = 137) and sporadic (n = 73) psoriasis families showed that the familial trios contribute strongly in the region around D19S425 (P = 0.004), while the comparably small subset of 73 sporadic trios has a stronger effect at the locus around D19S917 (P = 0.026). These studies confirm the existence of a psoriasis susceptibility locus on chromosome 19 and give first evidence for the existence of both susceptible and protective loci in this region. Analysis of a dense marker set from these refined regions will eventually allow identification of the underlying susceptibility alleles.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1034/j.1600-0625.2003.00040.x
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  • 2
    Electronic Resource
    Electronic Resource
    A genome-wide screen on the genetics of atopy in a multiethnic European population reveals a major atopy locus on chromosome 3q21.3 (2005)
    Oxford, UK : Munksgaard International Publishers
    Allergy 60 (2005), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.2005.00646.x
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  • 3
    Electronic Resource
    Electronic Resource
    Interleukin-10 promoter polymorphism IL10.G and familial early onset psoriasis (2003)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 149 (2003), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary  Background The anti-inflammatory cytokine interleukin (IL)-10 is considered to play a major role in the pathophysiology of psoriasis, which is characterized by an IL-10 deficiency. Systemic administration of IL-10 has been shown to be an effective therapy for psoriasis. The IL-10 promoter region contains a highly polymorphic microsatellite (IL10.G) and in a recent case–control study the IL10.G13 (144 bp) allele was found to be associated with familial early onset psoriasis (type 1 psoriasis) having a susceptible effect. Objectives As it is essential in multifactorial diseases to replicate findings before definite conclusions can be drawn, we decided to perform a follow-up study and to follow a genetic approach analysing allele transmission in families with a positive family history of psoriasis. Methods We studied 137 nuclear families (trio-design) comprising 456 individuals and genotyped the IL10.G marker. For comparison we also genotyped the microsatellite tn62 as a reference marker of the major psoriasis susceptibility locus on chromosome 6p21 (PSORS1). In the present study allele transmission was evaluated using the family-based association test (FBAT) and GENEHUNTER 2.0 based on the transmission/disequilibrium test. Results The G13 allele (144 bp) had a frequency of 24%, was present in 88 families and clearly showed an even transmission (FBAT, P = 0·753). In contrast, allele 3 (IL10.G9) (136 bp) had a frequency of 39%, was present in 110 families and was transmitted in 43 trios and remained untransmitted in 67 trios (FBAT, P = 0·026), thus showing preferential nontransmission. For the HLA-linked tn62-marker we obtained a P-value of 0·000 27 for allele 4 in the same study group. Conclusions In conclusion, we failed to confirm the susceptible effect of the G13 allele, but provide the first data for a protective effect of allele 3 (IL10.G9) for familial psoriasis. Our results suggest that the IL10.G polymorphism is not a major locus, but acts as a minor locus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2133.2003.05411.x
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