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1.
J Invest Dermatol ; 126(4): 740-5, 2006 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-16439971

RESUMEN

A major susceptibility gene for psoriasis is located in the major histocompatibility complex class I region on chromosome 6 very close to the HLA-Cw6 gene. We collected a cohort of 1,019 patients with chronic plaque psoriasis. The patients were typed for HLA-C and HLA-B. A total of 654 (64.2%) were HLA-Cw*0602 positive but 365 (35.8%) carried other HLA-C alleles. We confirmed that HLA-Cw*0602 positive patients have younger age of onset (17.5 vs 24.3 years, P<10(-10)), higher incidence of guttate and the eruptive type of psoriasis (P<0.0001), more frequent exacerbations with throat infections (P=0.01), higher incidence of the Koebner's phenomenon (P=0.01), and more extensive disease (P=0.03). A striking new finding was a diverging pattern of disease severity in HLA-Cw*0602 positive and negative patients depending on the age of onset of the disease (P=0.0006). HLA-Cw*0602 positive women also had more frequent remissions during pregnancy (P<0.0001). All types of nail changes were, however, more common in the Cw*0602 negative patients (P=0.003) and they more often had multiple types of nail lesions (P<0.0001). The three ancestral haplotypes of Cw*0602 all conferred an increase in odds ratio but showed no difference in any of the clinical features studied. Our findings indicate that the genetic factor on chromosome 6 has a strong influence on the phenotype of the disease, and underline that differences in clinical features of psoriasis may be to a large extent genetically determined.


Asunto(s)
Antígenos HLA-B/análisis , Antígenos HLA-C/análisis , Psoriasis/diagnóstico , Psoriasis/inmunología , Adolescente , Adulto , Cromosomas Humanos Par 6/genética , Enfermedad Crónica , Femenino , Antígenos HLA-C/genética , Humanos , Masculino , Embarazo , Psoriasis/genética , Índice de Severidad de la Enfermedad
2.
J Invest Dermatol ; 124(6): 1177-85, 2005 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15955092

RESUMEN

Psoriasis is a chronic inflammatory skin disease with overlapping subphenotypes. It has a strong complex genetic component, but has been problematic to identifying significant loci. We evaluated 1000 patients with chronic plaque psoriasis and documented several subphenotypes. Here we report results of genome-wide linkage scans for psoriasis genes in 238 Icelandic families with 874 patients. MHC linkage was confirmed with LOD score of 10.9. When the entire cohort was analyzed, two other loci with LOD scores of 2.5 and 1.5 were observed on 16q and 4q, respectively. Stratification into subphenotypes revealed additional loci with LOD scores exceeding or approaching significance. A LOD score of 5.7 appeared on 16q in PsA patients with analysis conditioned on parental inheritance. A LOD score of 3.6 on 4q was detected when disease occurred at or older than 17 y, our median cohort age. This locus was defined by a marker near one reportedly displaying significant linkage in a Chinese psoriasis population and near suggestive linkage in a Caucasian population. A LOD of 3.0 was observed on 10q when disease onset occurred in the scalp. Furthermore, clinical stratification either revealed or increased LOD scores when compared to unstratified analysis and some coincided with previous reports.


Asunto(s)
Ligamiento Genético , Psoriasis/genética , Edad de Inicio , Artritis Psoriásica/genética , Mapeo Cromosómico , Cromosomas Humanos Par 16 , Cromosomas Humanos Par 4 , Estudios de Cohortes , Femenino , Humanos , Islandia , Escala de Lod , Complejo Mayor de Histocompatibilidad/genética , Uñas/patología , Fenotipo , Psoriasis/epidemiología , Psoriasis/etiología , Psoriasis/patología , Dermatosis del Cuero Cabelludo/epidemiología , Piel/lesiones , Heridas y Lesiones/complicaciones
3.
J Invest Dermatol ; 118(2): 362-5, 2002 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11841557

RESUMEN

Psoriasis is associated with HLA-Cw6, and Caucasians who carry this allele have about a 10-fold increased risk of developing psoriasis. We have HLA-C typed 369 patients with familial psoriasis and compared the clinical features of the patients carrying HLA-Cw6 against those carrying other HLA-C types. Some striking clinical differences were observed between the two groups. Patients who are Cw6 positive had a lower age at onset (p=3x10(-7)). Cw6-positive women had an earlier disease onset than Cw6-positive men (p =0.02), but such a difference was not observed for the Cw6-negative patients. The guttate-type onset of psoriasis was mostly confined to this group (p=2x10(-4)) and persistent disseminated guttate-like papules were also predominantly observed in the Cw6-positive patients (p <10(-)4). The Cw6-positive patients also had more extensive plaques on their arms, legs, and trunk (p =0.001), more severe disease (p =0.003), higher incidence of the Koebner's phenomenon (p =0.005), reported more often that their psoriasis got worse during or after throat infections (p =0.02), and more often a favorable response to sunlight (p =0.008) In contrast, dystrophic nail changes were more common in the Cw6-negative patients (p =0.002) and also psoriatic arthritis, although this was not significant (p =0.135). It is concluded that patients with psoriasis have different clinical features depending on whether they are HLA-Cw6 positive or negative.


Asunto(s)
Psoriasis/inmunología , Psoriasis/patología , Adolescente , Adulto , Edad de Inicio , Anciano , Artritis Psoriásica/inmunología , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Enfermedades de la Uña/etiología , Psoriasis/complicaciones , Psoriasis/genética , Índice de Severidad de la Enfermedad , Caracteres Sexuales
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