Strong association of HLA-Cw6 allele with juvenile psoriasis in Polish patients
Introduction
Etiology of psoriasis vulgaris, a chronic inflammatory skin disease, is still unknown; both environmental and genetic factors are involved [1], [2]. Independent genome-wide searches mapped psoriasis susceptibility genes to several chromosomes [1], [2], [3]. Recently, large-scale gene expression study using microarray technique revealed 177 genes that were differentially expressed in involved psoriatic skin versus normal skin [4]. The strongest linkage and association was reproducibly described for Psor1 locus on chromosome 6p21.3, covering much of the human major histocompatibility complex, HLA [1], [2], [3]. Although results of many laboratories indicate HLA-Cw*0602 as a major psoriasis susceptibility allele [5], [6], [7], [8], [9], multiple other loci within the HLA region have also been implicated [2], [10], [11], [12], [13], [14]. The observed strength of HLA-Cw*0602-disease association was variable depending on ethnicity [5], [6], [7], [8], [9], [12], [15], sex [16] and age [16], [17], [18]. Therefore, we examined the association of HLA-C with psoriasis vulgaris in Polish patients who had not been tested so far in this respect by means of molecular HLA-C typing.
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Patients and controls
A total of 102 patients were diagnosed with psoriasis vulgaris in the Clinic of Venerology and Dermatology, interrogated for age at onset and for psoriasis in family, and blood samples were collected. Characteristics of the patients and their subgroups based on age at disease onset, is shown in Table 1. Control blood samples from 123 unrelated healthy blood donors, age-, sex- and ethnicity-matched with the patients, were kindly provided by the Blood Transfusion Centre in Wrocław. Informed
Results
Distribution of HLA-C alleles among 102 patients and 123 control subjects is given in Table 2(A). Significant differences in frequency were observed for two alleles: 4.7-fold increase of HLA-Cw*06 (P<0.0001, Pcorr<0.001) and 2.2-fold decrease of HLA-Cw*07 (P=0.0029, Pcorr=0.038) in psoriatic patients compared with the controls. Weak differences for the other three alleles, HLA-Cw*02, HLA-Cw*04 and HLA-Cw*16, were also observed, but lost significance after correction (Table 2A).
Subdivision of
Discussion
We have found association of psoriasis vulgaris with HLA-Cw*06, as reported for most but not all other human populations (see Section 1). Interestingly, the strongest association was in the earliest age at onset group (0–20 years) and it was statistically significant, not only in comparison with controls (Table 2B), but also with older (>21 years) patients (Table 3). Particularly striking was very high odds ratio (77.71; Pcor<0.001) for Cw*06 in group I. The highest frequency of HLA-Cw*06 in
Acknowledgements
The authors are indebted to Dr Ryszard Kozlowski, Director of the Regional Blood Transfusion Center in Wroclaw and his staff for their help in collecting blood from healthy blood donor volunteers. We also wish to thank Dr Beata Nowakowska for helpful comments to our data. This work was supported in parts by the State Committee for Research, Grant No. P05B 141 19; the Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Grant No. 14/2002; and by the Medical University of Wroclaw,
References (27)
- et al.
J. Invest. Dermatol.
(2002) - et al.
Am. J. Hum. Genet.
(1998) - et al.
J. Invest. Dermatol.
(2000) - et al.
J. Invest. Dermatol.
(2002) - et al.
J. Invest. Dermatol.
(1991) - et al.
Hum. Immunol.
(1992) - et al.
Immunol. Letts.
(2002) - et al.
Arch. Dermatol.
(2001) Br. J. Dermatol.
(2000)- et al.
Hum. Mol. Genet.
(2001)
J. Invest. Dermatol.
Br. J. Dermatol.
Dermatology
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A single nucleotide polymorphism -35kb T > C (rs9264942) is strongly associated with psoriasis vulgaris depending on HLA-Cw<sup>*</sup>06
2014, Human ImmunologyCitation Excerpt :It is in accordance with results showing that locus 6p21.3 (PSORS1), which contains HLA class I genes, is strongly associated with early-onset form of psoriasis vulgaris (type I in original classification by Henseler and Christophers). In contrast, type II PsV (late-onset) had no family history, and only weak significance of genes, including HLA-Cw∗06 from PSORS1, is documented for this psoriasis type [17], which was confirmed also in Poles [12]. The strong association between HLA-Cw∗06 and psoriasis vulgaris is known since 40 years [5].
Significance of association of HLA-C and HLA-E with psoriatic arthritis
2014, Human ImmunologyEmerging role for the killer-cell immunoglobulin-like receptors genotype, in the susceptibility of skin diseases
2013, Journal of Dermatological ScienceCitation Excerpt :These factors lead to an aggravated state of innate immunity characterized by the activity of NK cells, neutrophils, dendritic cells and keratinocytes [27]. As one of the strongest associations with psoriasis was found for a major histocompatibility complex HLA-Cw6 allele [28–32] (these individuals usually have a younger age of onset and more severe disease course), hence several studies have looked for associations of KIR genes with the development of psoriasis, but the collected data are sometimes discordant and do not provide a clear consensus. Some studies reported a statistically significant link of KIR2DS1 with the disease development, while others found no such gene association.
Gene for the activating natural killer cell receptor, KIR2DS1, is associated with susceptibility to psoriasis vulgaris
2004, Human ImmunologyCitation Excerpt :Psoriasis vulgaris is a multifactorial human skin disease [1–4]. The strongest genetic association was found with a major histocompatibility complex allele, HLA-Cw*06 [5–7], particularly in juvenile psoriasis [7–9]. Human leukocyte antigen (HLA)-C molecules are recognized by natural killer (NK) cell immunoglobulin-like receptors, KIR, encoded in the leukocyte receptor complex on chromosome 19q13.4 [10–14], and fall into two groups differing in amino acid positions 77 and 80 in the α1 domain.