Article

A Susceptibility Gene for Psoriatic Arthritis Maps to Chromosome 16q: Evidence for Imprinting

deCODE Genetics, Reykjavik, Iceland.
The American Journal of Human Genetics (Impact Factor: 10.99). 01/2003; 72(1):125-31. DOI: 10.1086/345646
Source: PubMed

ABSTRACT Several genetic loci have been reported for psoriasis, but none has been specifically linked to psoriatic arthritis (PsA), a condition that affects >10% of patients with psoriasis. A genetic component for PsA is suggested by segregation within families and high concordance among identical twins. We performed a linkage scan to map genes contributing to PsA. We identified 178 patients with PsA out of 906 patients who were included in our genetic study of psoriasis. Using a comprehensive genealogy database, we were able to connect 100 of these into 39 families. We genotyped the patients using a framework marker set of 1,000 microsatellite markers, with an average density of 3 cM, and performed multipoint, affected-only, allele-sharing linkage analysis using the Allegro program. On the basis of the initial results, we genotyped more markers for the most prominent loci. A linkage with a LOD score of 2.17 was observed on chromosome 16q. The linkage analysis, conditioned on paternal transmission to affected individuals, gave a LOD score of 4.19, whereas a LOD score of only 1.03 was observed when conditioned for maternal transmission. A suggestive locus on chromosome 16q has previously been implicated in psoriasis. Our data indicate that a gene at this locus may be involved in paternal transmission of PsA.

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    • "genetics underlying HLA susceptibility in T1D may exhibit parental inheri - tance ; Pani and colleagues suggest that the maternal HLA - DQ2 or DQ8 alleles are risk factors for T1D ( Pani et al . , 2002 ) . For psoriatic arthritis , genetic linkage analysis suggests that there is imprinted transmission at chromosome 16q that is of paternal origin ( Karason et al . , 2003 ) ."
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    • "genetics underlying HLA susceptibility in T1D may exhibit parental inheri - tance ; Pani and colleagues suggest that the maternal HLA - DQ2 or DQ8 alleles are risk factors for T1D ( Pani et al . , 2002 ) . For psoriatic arthritis , genetic linkage analysis suggests that there is imprinted transmission at chromosome 16q that is of paternal origin ( Karason et al . , 2003 ) ."
    [Show abstract] [Hide abstract]
    ABSTRACT: Autoimmune diseases are a range of diseases in which the immune response to self-antigens results in damage or dysfunction of tissues. Autoimmune diseases can be systemic or can affect specific organs or body systems. For most autoimmune diseases there is a clear sex difference in prevalence, whereby females are generally more frequently affected than males. In this review, we consider gender differences in systemic and organ-specific autoimmune diseases, and we summarize human data that outlines the prevalence of common autoimmune diseases specific to adult males and females in countries commonly surveyed. We discuss possible mechanisms for sex specific differences including gender differences in immune response and organ vulnerability, reproductive capacity including pregnancy, sex hormones, genetic predisposition, parental inheritance, and epigenetics. Evidence demonstrates that gender has a significant influence on the development of autoimmune disease. Thus, considerations of gender should be at the forefront of all studies that attempt to define mechanisms that underpin autoimmune disease.
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    • "It has been proposed that two forms of psoriasis can be recognized (type I and type II), with type I psoriasis, characterized by onset age p40 years, being more likely to be familial, severe, and strongly associated with HLA-Cw6 (Henseler and Christophers, 1985; Stuart et al., 2002). The prevalence of psoriasis is approximately the same in males and females, though PsA has been suggested to be preferentially transmitted from male parents (Rahman et al., 1999; Karason et al., 2003). Substantial genetic epidemiological data, including studies of twins, pedigrees, and relatives of unrelated index patients suggest that psoriasis is multifactorial, that is, influenced by multiple genes as well as environmental factors including stress, trauma, and infections, notably Streptococcal pharyngitis (Lomholt, 1963; Watson et al., 1972; Gudjonsson and Elder, 2007a). "
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