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1. Introduction
Psoriasis is an immune-mediated skin disease affecting 2-3% of the general population. The most common companion to psoriasis is psoriatic arthritis (PsA), a chronic inflammatory arthritis that affects approximately one-third of psoriasis patients. Both are the main poles of what is currently known as psoriatic disease [1]. The underlying mechanisms of psoriatic disease appear to involve complex interactions between genetic and environmental factors leading to alterations in immunological and inflammatory pathways involving the innate and adaptive immune responses [1].
The human leukocyte antigen (HLA) class I region encodes essential proteins for immune recognition [2]. Within this region, several genes are of particular importance for susceptibility as well as for the phenotypic differentiation of psoriatic disease [2]. Thus, the HLA-C
Apart from the well-known association between HLA-C
Although psoriatic disease is frequently accompanied by cardiovascular comorbidity [7], the potential genetic connections between this comorbidity and psoriatic disease have received little attention. Eirís et al. demonstrated that genetic variations in the IL12/23 pathway were important not only to define both the risk and severity of psoriatic disease but also for the risk of certain comorbidities such as type 2 diabetes mellitus [8]. In another study, Inerot et al. found endocrine disorders in 9% of HLA-Cw6-negative psoriasis patients compared to 1% of those Cw6 positive. In addition, no Cw6 patient was diabetic compared to a 5% overall prevalence of diabetes in the Swedish general population [9].
Furthermore, we do not know whether the genetic pathways to both cardiovascular comorbidity and psoriatic disease are common or different. However, a certain degree of commonality between psoriatic disease and some cardiovascular comorbidities as regards genes/proteins, biological processes, and inflammatory pathways has recently been highlighted [10]. Another study demonstrated shared genes between psoriasis and increased risk of dyslipidemia, hypertension, and cardiovascular disease [11]. Yet, a German study suggested that the genetic architecture of both psoriatic disease and cardiometabolic traits is largely distinct [12].
Genetic relationship studies between cardiometabolic risk factors and psoriatic disease are scarce, but they may contribute to refining the healthcare for these patients. Here, we aimed to analyze the role of the HLA-C
2. Patients and Methods
This cross-sectional observational study included 400 consecutive patients with psoriatic disease, diagnosed and followed up in a collaborative dermatology-rheumatology unit at a tertiary center in northern Spain. To study the effect of the HLA-C
In summary, clinical, analytical, sociodemographic, radiological, and treatment variables were collected. The HLA-C
In terms of laboratory data, hemogram, blood, and urine biochemistry, immunological parameters (rheumatoid factor, antinuclear antibodies, and HLA-C
Information was collected on the family history of the disease. For the purposes of this study, patients were divided into early-onset versus late-onset disease based on a cutoff age of 40 years.
2.1. HLA-C Profile Testing
To determine HLA-C typing, we followed the same methodology previously used by our group [6]. Briefly, DNA was isolated from lymphocytes by standard procedures. HLA-C alleles were specifically amplified with a combination of the sense primer SV1 (exon 2, codon 45) and the antisense primer SV2 (exon 3, codon 182). The spanning sequences (680 base pairs) containing the hypervariable regions of HLA-C exons 2 and 3 were used to examine the HLA-C alleles. Polymerase chain reaction conditions for the amplification of exons 2 and 3 were 95°C for 30 seconds and 67°C for 50 seconds (50 cycles), with an initial denaturation step of 98°C for 1 minute and a final extension step of 70°C for 5 minutes. The specificity of the PCR-SSOP (polymerase chain reaction sequence-specific oligonucleotide probe) method was checked by using B lymphoblastoid cell lines as positive controls for the HLA-C alleles.
2.2. Statistical Analysis
Central and dispersion measures were analyzed. Differences between qualitative variables were measured by a Pearson’s chi-square and Fisher’s exact test. To test the differences between quantitative variables, parametric (Student’s
3. Results
3.1. Summary of Study Population
The study included 215 men (53.8%) and 185 women (46.2%), with a mean age of
Table 1
Disease features of the study population.
Feature | |
Mean age, years (SD) | |
Mean age at psoriasis onset, years (SD). | |
Mean time of disease evolution, years (SD) | |
Men, | 215 (53.8) |
Women, | 185 (46.2) |
Mean PASI (SD) | |
280 (70) | |
120 (30) | |
Psoriasis family history, | 168 (42) |
160 (40) | |
Nail involvement, | 240 (60) |
PsA, | 93 (23.3) |
Mean waist circumference, cm (SD) | |
Mean BMI (SD) | |
Hypertension, | 80 (20) |
Dyslipidemia, | 64 (16) |
Obesity, | 120 (30) |
Smokers, | 72 (18) |
Diabetes, | 42 (10.5) |
CHD, | 25 (6.3) |
Total cholesterol, mg/dl (SD) | |
HDL-C, mg/dl (SD) | |
LDL-C, mg/dl (SD) | |
TG, mg/dl (SD) | |
Blood glucose, mg/dl (SD) | |
Topical/phototherapy treatment, | 180 (45) |
Nonbiologic systemic treatment, | 248 (62%) |
Biological therapy, | 172 (43) |
SD: standard deviation;
3.2. Analysis by Gender
With respect to women, men showed significant differences in serum HDL-C levels (
3.3. Analysis of the PsA Population
Overall, 93 (23.3%) patients met CASPAR criteria for PsA (47 men and 46 women, mean age
3.4. Analysis of Cardiovascular Risk Factors
Although most cardiovascular comorbid factors were significantly more prevalent in subjects with disease onset above 40 years in bivariate analyses (
3.5. Analysis by HLA-C
Of the 400 patients in the study, 160 were HLA-C
Table 2
Distribution of variables between HLA-C
Variable | HLA-C | HLA-C | |
Age (yrs), mean (SD) | 43.3 (13.8) | 48 (15) | <0.05 |
Age (yrs) at psoriasis onset, mean (SD) | 22 (14.8) | 32.6 (17.6) | <0.05 |
Disease duration (yrs), mean (SD) | 19.2 (14.3) | 15.3 (14.7) | NS |
Men, | 88 (55) | 127 (53) | NS |
Women, | 72 (45) | 113 (47) | NS |
PsA, | 34 (21.3) | 59 (24.6) | NS |
Psoriasis family history, | 88 (55) | 80 (33.3) | <0.05 |
80 (50) | 80 (33.3) | <0.05 | |
Total cholesterol, mean (SD) | 203.2 (41.8) | 206.7 (43.4) | NS |
HDL-C, mean (SD) | 54.1 (15.4) | 53.7 (14.8) | NS |
LDL-C, mean (SD) | 125.6 (36.7) | 129.5 (36) | NS |
TG, mean (SD) | 125.1 (75.9) | 128.7 (86.5) | NS |
Glucose, mean (SD) | 97.5 (32.6) | 103.8 (33.9) | NS |
BMI, mean (SD) | 27 (4.4) | 28.2 (4.8) | <0.05 |
Waist perimeter (cm), mean (SD) | 94.4 (13.7) | 98.3 (13.8) | <0.05 |
Hypertension, | 22 (13.8) | 58 (24.2) | <0.05 |
Dyslipidemia, | 21 (13.1) | 43 (17.9) | NS |
Obesity, | 42 (26.3) | 78 (32.5) | NS |
Smoker, | 32 (20) | 40 (16.7) | NS |
CHD, | 8 (5) | 17 (7.1) | NS |
Topical/photo therapy, | 48 (30) | 132 (55) | <0.05 |
Systemic treatment, | 88 (55) | 160 (66.7) | NS |
Biologics, | 90 (56.3) | 82 (34.2) | <0.05 |
Yrs: years; SD: standard deviation;
Figure 1 offers a summary view of the clinical phenotype associated with the HLA-C
4. Discussion
In this single-center study that included a substantial number of patients with psoriatic disease, we have confirmed findings from previous studies related to an association between the HLA-C
The HLA-C
In any case, the most striking and novel findings drawn from our study refer to the association between HLA-C
We have also seen how HLA-C
Our study has the limitations of most observational studies with retrospective data collection. Therefore, we cannot discern the direction of the associations found in it, and the bias of false causality cannot be reliably ruled out. For example, HLA-C
5. Conclusion
We have confirmed the well-known association between HLA-C
Ethical Approval
This study was approved by the Ethics Committee of Clinical Investigation of Principado de Asturias (ref. HUCA 68/19).
Consent
All participants gave their written informed consent.
Authors’ Contributions
All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Rubén Queiro and Pablo Coto. The first draft of the manuscript was written by Rubén Queiro, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Abstract
The human leukocyte antigen-C
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1 Rheumatology Division, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain; ISPA Translational Immunology Division, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain; Oviedo University School of Medicine, Spain
2 Dermatology Division, Hospital Vital Alvarez Buylla, Mieres, Asturias, Spain
3 Rheumatology Division, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain