Platelet polymorphism rs5918T > C in the integrin B3 gene modulates comorbidities in patients with psoriasis

Abstract

Psoriasis Vulgaris is a complex multifactorial dermatological disease, with various genetic and environmental factors implicated in the onset and progression of the disease and comorbidities. Cardiovascular disease (CVD) and metabolic syndrome are essential psoriasis comorbidities that suggest a potential hypercoagulable background of the disease. To better understand the link between psoriasis, hypercoagulation and comorbidities, we investigated the prothrombotic polymorphism rs5918T > C in integrin B3 (ITGB3) in 102 patients diagnosed with psoriasis and 97 healthy controls, all Caucasian. The patients, carriers of rs5918T > C polymorphism, were compared with non-carriers for metabolic risk factors related to metabolic syndrome and CV disease. Our results revealed that the incidence of ITGB3rs5918(C) allele carriage was only slightly increased in psoriatic patients compared to healthy controls (20.6% vs 18.6%), and psoriatic patients with the polymorphism showed an increased incidence of metabolic risk factors. Dyslipidemia, high triglycerides (42.9% vs 27.5%), high cholesterol (66.7% vs 45.5%) and low High Density Lipoprotein (HDL) (47.6% vs 32.8%) were significantly more prevalent (p = .019) among psoriatic carriers of the rs5918(C) polymorphism compared to psoriatic non-carriers. The incidence of metabolic syndrome was significantly higher among polymorphism carriers (52.4%) compared to non-carriers (20.5%) within the psoriatic patient group (p = .014), whereas CVD incidence was higher but non-significantly. The carriage of ITGB3rs5918(C) polymorphism in patients with psoriasis was associated with a higher risk of metabolic syndrome and dyslipidaemias and a higher but non-significant prevalence of CVD compared to non-carriers. However, the frequency of this polymorphism was similar in psoriasis patients and healthy controls.

Keywords:

• Psoriasis
• metabolic syndrome
• cardiovascular disease
• ITGB3 rs5918T > C
• polymorphism

Introduction

Psoriasis Vulgaris is a complex, chronic, multigenic, immune-mediated condition with a heavy inflammatory component affecting the skin, joints, and other tissues and organs [1]. Psoriasis Vulgaris is a disease with multiple comorbidities [2]. Studies have demonstrated that apart from psoriatic arthritis and Crohn’s disease, which share genetically based mechanisms of pathology, among psoriatic patients there is a higher risk of developing cardiovascular disease (CVD): acute myocardial infarction, stroke and cardiometabolic disease [3,4]. The increased incidence of CVD results from common cardiovascular risk factors, that is, hypertension, dyslipidemia, hypercholesterolemia, obesity and insulin resistance – all aspects of metabolic syndrome [4]. Nonetheless, the mechanisms underlying the association between psoriasis and metabolic syndrome remain unknown, despite numerous studies on the association between genetic and environmental risk factors [5,6].

The aetiology of CVD risk in patients with psoriatic disease continues to be the subject of numerous studies. A potential causal mechanism to this association may be a compromised metabolic status which triggers inflammatory mediators and procoagulant factors implicated in psoriasis and vascular pathogenesis, contributing to a comorbid condition in those patients [7,8]. There is evidence for systemic inflammation in psoriasis [9] and an association of psoriasis with early coronary artery disease [4]. Psoriasis has a multifactorial genetic basis [10] demonstrated by epidemiological studies and familial recurrence [11], involving various inherited susceptibility polymorphic alleles. These facts lead us to assume that specific polymorphisms associated with cardiovascular risk, proinflammatory and prothrombotic conditions may contribute to the higher risk of developing psoriasis and may influence its comorbidities.

One such candidate is rs5918T > C single nucleotide polymorphism (SNP) in the ITGB3 gene [12]. The Rs5918T > C polymorphism in the ITGB3 gene is due to a substitution of thymine with cytosine (T/C) at position 1565 in exon 2 of the ITGB3 gene, resulting in the replacement of leucine with proline [13]. Integrin B3 (ITGB3) is a beta subunit of glycoprotein αIIbβ3 in the platelet membrane, serving as a receptor for fibrinogen and Von Willebrand factor (VWF) [13]. Initial interaction via adhesion with extracellular surfaces, for example, a fibrin clot (mediated via the αIIbβ3 integrin receptor), triggers platelet activation. ITGB3’ is a component of αIIbβ3 and is found in high abundance on the surface of the platelet membrane (∼80,000 copies as determined by monoclonal antibodies). Activation by external stimuli (ADP, thrombin, adrenaline, VWF) results in the expression of a higher number of integrin molecules on the cell surface and conformational changes in the receptor, increasing its affinity for fibrinogen binding. The activated platelet increases the number of ITGB3 on its membrane by about 50% compared to the non-activated one [14]. Ligand binding transduces signals from the extracellular environment to the cell. These bidirectional signalling events are subject to active regulation, and their disruption can lead to uncontrolled platelet aggregation, subsequent thrombosis, and pathological conditions such as ischemic CVD.

ITGB3 is a central mediator of platelet aggregation [15] and thus a vital element of blood coagulation [16,17]. The carriage of the polymorphism rs5918 (CC + CT), as homozygous and heterozygous variants, is roughly 15% in a healthy population [18]. This polymorphism contributes to an increased risk of coronary disease [15], coronary stent thrombosis [19], myocardial infarction [20] and stroke [21] and higher resistance to the antithrombotic effects of aspirin [22].

In this study, we single out the role of ITGB3 rs5918T > C polymorphism in the development of psoriasis and its comorbidities.

We analyzed the risk of CVD and metabolic syndrome in psoriatic carriers of ITGB3 rs5918(C) compared to non-carriers in Caucasian patients with plaque psoriasis.

Apart from rs5918(C), the following polymorphisms are also known to contribute to the risk of CVD and prothrombotic risk: polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C; Factor XIII (FXIII V34L); Plasminogen activator inhibitor 1 (PAI-1 4 G/5G); Apolipoprotein E (Apo E) E2/E3/E4; Apolipoprotein B (Apo B R3500Q); Prothrombin G20210A; Factor V Leiden (FVL) (G1691A); FV R2 haplotype (H1299R); beta-fibrinogen (FGB)-455 G > A and Angiotensin-converting enzyme (ACE) 287 bp insertion/deletion (I/D). Since these factors could influence our investigation of the effect of ITGB3 rs5918(C) on comorbidities in psoriatic patients, we excluded all genetic carriers of other abovementioned mutations from our analysis. This enabled us to compare CVD and metabolic syndrome comorbidities in a group of psoriatic patients who only carry polymorphism ITGB3 versus the group of patients non-carriers of rs5918(C) and not any other polymorphisms with CV risk mentioned above.

So far, there are no studies on the carriership of the ITGB3 rs5918(C) polymorphism in psoriatic patients and its contribution to CV comorbidities.

Subjects and methods

Institutional review board statement

Written informed consent was obtained from each patient and control subject. The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Ethics Committee of Medical University Pleven (No. 662 KENID, protocol No. 57/29.06.21).

Data collection

This study was conducted in the Clinic of Dermatology & Venereology, University Hospital (UMBAL) – Pleven, Bulgaria, and the Biochemistry Department of the Medical University of Pleven, Bulgaria. The study included 102 unrelated patients with clinically manifested plaque psoriasis, above 18 years, having provided signed informed consent and enrolled between January 2017 and March 2021.

The diagnosis was made via skin examination and biopsy. The patients with systemic inflammation, tuberculosis, Hepatitis B, Hepatitis C and HIV infection we excluded from the study. Ninety-seven unrelated, gender and age-matched, healthy individuals with no psoriasis disease were selected for the control group. All patients and controls were Caucasian. They were screened for genotype ITGB3 rs5918T > C carriage and cardiovascular risk factors.

The anthropometric and laboratory data were collected from the patients and controls.

Clinical assessment and anthropometry

Psoriasis Area Severity Index (PASI) score was used as an indicator for the measurement of the severity of psoriasis. PASI scores range from 0 to 72. They reflect the degree of the skin surface affectedness and determine the severity of the disease [23]. Disease severity according to PASI score is determined as follows: mild psoriasis (PASI < 3), moderate (PASI 3$-$10), severe psoriasis (PASI 10$-$20, very severe psoriasis (PASI > 20). For anthropometry, height (in cm) and weight (in kg) were measured to calculate Body Mass Index (BMI) as weight (kg)/height (m) squared.

Sample collection and SNP genotyping

DNA samples were taken from subjects with clinically manifested psoriasis and control subjects with no psoriasis, and were examined for the carriage of rs5918T > C in the ITGB3 genotype. Venous blood was acquired in 10-mL coated EDTA serum vacutainers. The salting out method was used for DNA extraction from venous blood.

A strip assay (ViennaLab Diagnostics, Vienna, Austria) was applied to identify the ITGB3 rs5918 T > C polymorphism. Carriage of other polymorphisms associated with a higher risk of CVD and thrombosis comorbidities was also investigated via the same assay to rule out their contribution to the result.

Strip assay is a human diagnostic tool for genotyping mutations and polymorphisms (SNPs, deletions, insertions) based on polymerase chain reaction (PCR) and reverse-hybridization to allele-specific oligonucleotide probes immobilized on test strips [24]. The CVD Strip Assay Kit options detect variants in the following genes: rs5918T > C ITG B3; FVL G1691A; FV R2H1299R; FII G20210A; MTHFR C677T; MTHFR A1298C; FXIII V34L; PAI-1 4 G/5G; Apo B R3500Q; Apo E E2/E3/E4; FGB-455 G > A; ACE 287 bp I/D. Strip technology is based on the reverse hybridization of biotinylated PCR products. It combines probes for variants and controls in a parallel array of allele-specific oligonucleotides, works with immobilized oligos on a test strip, and generates test results by enzymatic colour reaction easily visible to the naked eye [19]. The Hardy-Weinberg equilibrium was used to calculate the genetic variation in a population. The allele frequencies of the C and T alleles in the patient groups compared to those in the control group were calculated according to Hardy-Weinberg.

Laboratory assays

Biochemical indicators (blood sugar, total cholesterol, HDL-cholesterol, triglycerides and C-reactive protein

(CRP) were routinely determined in the Certified Central Clinical Laboratory of UMBAL – Pleven. All testing was performed in the morning after a 12-h overnight fast. An average of two to three fasting blood samples collected on separate days were used to determine lipids, blood glucose and other metabolites.

Selection of groups of patients for analysis

Group for evaluation of rs5918T > C polymorphism carriage in psoriatic patients

A group of 102 patients was used to analyze the carriage of rs5918(C) polymorphism compared to controls.

Groups for the evaluation of CVD and metabolic risk parameters in psoriatic carriers and psoriatic non-carriers of rs5918(C) polymorphism

Twelve known polymorphisms were investigated and excluded from the patient group analysis to avoid the influences of other common polymorphisms for CVD risk. The psoriatic patients who were identified as carriers of these polymorphisms were extracted from the total patients’ group, and the non-carriers were conventionally designated as non-carriers of polymorphism. They were used as a negative control to compare with the psoriatic patient carriers of the rs5918 (C) polymorphism for the incidence of comorbidities. This negative control group of non-carriers was formed to avoid the contribution of polymorphisms with a known risk for CVD and metabolic syndrome.

Data analysis

Data are presented as mean values with standard deviations (±SD). Statistical analysis was performed with Statistical Package for Social Sciences (SPSS) version 23.0. and Microsoft Excel 2019. SPSS 23 was used for the statistical analysis of the polymorphism carriage to calculate Chi-squared, Odds Ratio (OR) and Exact Fisher test values. In all statistical tests, differences were considered significant at the p < .05 level.

Results

Anthropometric and clinical data

The primary anthropometric and clinical data of patients are presented in Table 1. The patients and controls were adjusted by age and gender (not presented). Occurrences of BMI Score > 30 were significantly more frequent among patients compared to the controls. The mean PASI score (26.29) of the entire group of patients was above 20 in the ‘very severe’ category. Psoriasis patients had the following comorbidities: hypertension 63.7%, Metabolic syndrome 38.4%, CVD 32.35%, psoriatic arthritis 34.3% and Diabetes Type II 19.6%.

Table 1. Anthropometric and clinical data, mean age, Body mass index (BMI), psoriasis area severity index (PASI), cardiovascular disease (CVD), hypertension, diabetes type II, psoriatic arthritis and metabolic syndrome of the patients included in the study and the mean age and BMI of controls.

Parameters	Patients mean ± SD	Controls means ± SD
Number of subjects	102	97
Mean age (years)	53.87 ± 12.60	52.40 ± 14.82
Age at diagnosis (years)	36.24 ± 15.52
BMI (kg/m^2)	29.17 ± 5.63	24.35 ± 3.90
PASI score	26.29 ± 9.21
Hypertension	61 (59.8%)
Diabetes Type II	20 (19.61%)
CVD	33 (32.35%)
Metabolic syndrome	39 (38.4%)
Psoriatic arthritis	35 (34.3%)

Prevalence of the ITGB3 rs5918(C) allele

The results of DNA analysis for the prevalence of the ITGB3 rs5918(C) allele, OR, Chi-squared, 95% confidence interval and Fisher exact test are presented in Table 2.

Table 2. Prevalence of ITGB3 rs5918(C) genotype, allele frequency, odds ratio (OR), Chi-squared, 95% confidence interval and Fisher’s exact test in psoriatic patients versus controls.

Genotypes and Allele frequencies of ITGB3 rs5918T > C	Prevalence in patients (%)	Prevalence in controls (%)	Chi-squared (χ2)	OR	95% Confidence interval	Fisher’s exact test
Heterozygous + homozygous (CT + CC)	21 (20.6)	18 (18.6)	0.2452	1.24621	0.5709 − 2.3250	p = . 518
Homozygous (TT)	81 (79.4)	79 (81.4)
T	90 (88.5)	91 (90.72)				p = .506
C	12 (11.5)	9 (9.28)				p = .314

The homozygous mutant genotype is rare in the general population; usually, it is less than 1%. Our DNA analysis revealed two homozygous patients with the mutant version of the allele and none among the controls. Thus, the carriage of the rs5918(C) polymorphism was calculated as a sum of the prevalence (20.6%) of rs5918(CC) and rs5918(CT) and presented as a whole group of C allele carriers. Both homozygous and heterozygous carriage contribute to the altered ITGB3 conformation.

The relationship between carriership of the variant ITGB3 rs5918C polymorphism and psoriasis was non-significant, as evident from the data on the polymorphism carriage in the patients with psoriasis versus controls (Chi-squared 0.2452, OR 1.2461, p = .518) (Table 2).

The allele frequencies of the (C) and (T) alleles in the group of patients compared to those in the control group were calculated according to Hardy-Weinberg equation and were, respectively, in patients rs5918(C) (11.5%) and rs5918(T) (88.5%), and in controls, 9 (9.28%) and 91 (90.72%) (Table 2). According to gnomAD database for the total population, the allele frequency was found to be 0.1223 (12.23%) [25].

Presentation of a selected group of non-carriers of the ITGB3 rs5918C polymorphism and common CVD polymorphisms

The allele frequencies were investigated with the strip analysis method, which resulted in 12 polymorphisms associated with CV risk. We extracted all the patients who were carriers of the polymorphisms related to thrombotic and cardiovascular risk from the cohort of patients with psoriasis and thus selected a cohort of patients, non-carriers, constituting 44 patients. The clinical/laboratory presentation of the patients’ group without the allele variant was compared to that of patients carriers of the rs5918(C) polymorphism (Table 3).

Table 3. Incidence rates for psoriatic patients carriers of the ITGB3 rs5918(C) allele versus non-carriers of the polymorphism for high BMI, hyperglycemia, triglyceridemia, low HDL, hypercholesterolemia, dyslipidemia, hypertension, high CRP, PASI score >20, cardiovascular disease, metabolic syndrome and total comorbidities.

Parameters	Carriers of ITGB3 rs5918(C) Mean ± SD (%)	Non-carriers of ITGB3 rs5918(C) Mean ± SD (%)	Chi-squared	Odds ratio (OR)	p Value
Number of subjects	21	44
Mean age (years)	55.65 ± 9.96	54.27 ± 18.41			0.741
Patients with BMI ≥ 30 kg/m^2	11 (52.4)	19 (44.2)	0.9	1.4	.478
Patients with BMI ≥ 25 kg/m^2	19 (95)	35 (81.4)	2.1	4.3	.110
Patients with hyperglycemia	7 (33.3)	11 (25.0)	1.1	1.50	.322
Patients with triglyceridemia	9 (42.9)	11 (27.5)	1.98	1.5	.034
Patients with low HDL	10 (47.6)	13 (32.8)	3.8	3.4	.0385
Patients with hypercholesterolemia	15 (66.7)	20 (45.5)	2.29	2.167	.050
Patients with dyslipidemia	18 (85.7)	28 (63.6)	3.4	2.7	.019
Patients with Hypertension	14 (66.7)	26 (59.1)	0.701	1.4	.322
Patients with Diabetes Type II	5 (23.8%)	4 (9.1%)	2.582	3.125	. 214
Patients with high CRP	10 (47.6.)	14 (33.3)		1.8.0	.511
CRP (mg/L)	7.18 ± 7.27	5.05 ± 16.71			.330
Patients with PASI scores > 20	19 (92.5)	32 (73.3)	1.97	4.3	.210
PASI score	28.03 ± 12.36	25.90 ± 8.33			.0421
Cardiovascular disease	7 (33.3)	12 (27.3)		1.20	.721
Metabolic syndrome	11 (52.4)	9 (20.5)	6.8	4.3	.058
Psoriatic arthritis	6 (28.7)	12 (27.3)		1.00	.531
Total comorbidities related to CVD	33/21 (1.6)	45/44 (1.02)	4.8		.050

Clinical and laboratory data

To evaluate the importance of the ITGB3 rs5918T > C polymorphism on comorbidities, and particularly CV risk and metabolic syndrome, the clinical and laboratory data of psoriatic patients with the ITGB3 rs5918T > C genotype were compared with the cohort of 44 patients with no polymorphism (after extraction of the patients who are carriers of procoagulant and CVD risk polymorphisms).

The clinical and laboratory data of psoriatic patients carriers of the ITGB3 rs5918(C) allele, and non-carriers of CVD polymorphism are presented in Table 3.

The carriers and non-carriers of polymorphism presented with a mean age of diagnosis and fasting blood glucose levels of almost identical values (Table 1). There were also similar BMI values in the carriers and non-carriers (29.94 kg/m² vs 28.97 kg/m²). The patients with the ITGB3 rs5918(C) polymorphism displayed elevated PASI (28.74 vs 24.90; p = .421) (Table 3) but non-significantly. The number of patients presenting high PASI scores (>20) was higher among the carriers of the ITGB3 rs5918(C) polymorphism compared to the patients, non-carriers (92.9% vs 73.3%). The CRP values in the patients carriers of the ITGB3 rs5918(C) allele were higher, but not significantly, versus the non-carriers (7.2 mg/L vs 5.1 mg/L).

The number of patients with hyperlipidemia was significantly higher among the polymorphism carriers. The number of patients carriers of rs5918(C) with high triglycerides was significantly higher (42.9%) than that among non-carriers (27.5%). High total cholesterol was found in carriers (66.7%) versus 45.0% among non-carriers. Low HDL was found in 47.2% of the carriers of rs5918(C) polymorphism versus 32.8% in non-carriers (Table 3). The total number of patients with dyslipidemia was significantly higher among the carriers of rs5918(C) (88.0%) versus 63.6% among the non-carriers. The prevalence of the clinical parameter ‘metabolic syndrome’ was significantly higher among the carriers of polymorphisms (52.4%) compared to non-carriers (20.5%), while the prevalence of hypertension, ischemic heart disease, heart failure and psoriatic arthritis was slightly elevated in carriers in comparison with non-carriers.

Discussion

Psoriasis is widely considered a multifactorial disease caused by polygenic interactions between different genomic loci and environmental risk factors [1,2]. Epidemiological and genetic studies confirm that polymorphisms and environmental factors, such as obesity, unhealthy nutrition, low physical activity and smoking, contribute to specific psoriasis comorbidities. They are associated with an inflammatory component and endothelial dysfunction leading to cardiovascular/cardiometabolic disease.

Our study aims to investigate the ITGB3 rs5918(C) allele carriage in patients with psoriasis to shed some light on its impact on psoriasis and comorbidities related to cardiovascular risk and metabolic syndrome, which are among the most critical comorbidities of psoriasis, particularly important in patients with a higher BMI.

As a subunit of glycoprotein IIb/IIIa, ITGB3 is a key receptor of platelets that binds fibrinogen and mediates platelet aggregation and blood clotting [16]. The rs5918(C) polymorphism alters the ITGB3 conformation and the orientation of the ligand-binding region and contributes to an elevated risk of CVDs, even in heterozygous carriers [18].

Carriage of the ITGB3 rs5918 T > C(PlA2) allele was found to be significantly associated with acute coronary thrombosis, particularly in patients diagnosed with sudden cardiac death, with an increased association being observed in patients under 60 years of age [26]. These data indicate that rs5918(C) carriers have an increased association with platelet-mediated thrombotic cardiac events, which is essential for our cohort of patients as most of them (70%) are under 60 years old.

Nonetheless, in our study, the prevalence of the ITGB3 rs5918(C) polymorphism in patients with psoriasis was only 2% higher than in controls, indicating no influence on the development of psoriasis itself. Indeed, we noticed that the level of cardiometabolic factors was somewhat higher among the carriers of this polymorphism. This was why we focused our study on examining the contribution of this genetic polymorphism on complex inflammatory comorbidities due to the cumulative and potential effect on psoriasis comorbidities.

Moreover, our previous study on the impact of psoriasis and its comorbidities in carriers of another common cardiovascular polymorphism, MTHFR C677T, demonstrated a higher risk of psoriasis and metabolic syndrome in obese male patients [27,28]. The next step was to investigate the impact of another cardiometabolic polymorphism on the development of comorbidities in psoriasis patients carrying the ITGB3 rs5918(C) allele compared to non-carriers when excluding other known CVD risk or metabolic syndrome polymorphisms.

In our relatively small group of 102 patients, this polymorphism was found significant only in the evaluation of the metabolic parameters. The statistical analysis indicates association of the ITGB3 rs5918(C) polymorphism with incidences of trigliceridemia, hypercholesterolemia and HDL in psoriatic patients, factors contributing to the development of CVD and metabolic syndrome. Although the frequency of hyperglycemia and hypertension in psoriatic patients carriers of the ITGB3 rs5918(C) allele did not reach the statistical significance level, the combination of these factors with the dyslipidemic factors and BMI produces a higher risk for metabolic syndrome in the carriers of the ITGB3 rs5918(C) allele compared to the non-carriers in the investigated group of patients.

The higher prevalence of trigliceridemia, hypercholesterolemia and hyperglycemia in patients carriers of polymorphism merits special attention, as these are risk factors for other diseases apart from metabolic syndrome, namely CVD [29], neurodegenerative disease [30], pregnancy complications [31], Diabetes Type II and others.

Indeed, there was no significant increase in cardiovascular events in the patients carrying the ITGB3 rs5918(C) polymorphism. It was not expected based on the literature presenting a high incidence of CVD in psoriatic patients and the occurrence of this polymorphism in patients with CVD [32].

The relationship between the carriage of ITGB3 rs5918(C) and cardiometabolic risk has been investigated in numerous studies with controversial results [15, 17, 19–21, 32]. For example, the prevalence of this polymorphism in patients with myocardial infarction was found with OR values in the range of 0.570–5.935 [33]. There was an association between this glycoprotein polymorphism and the stage of atherosclerosis in the abdominal aorta [34] and atherosclerotic plaque thickness [35], factors suggesting cardiometabolic risk. The interrelationship between increased cardiometabolic risk factors, inherited and environmental, in patients with psoriasis is still highly debated, suggesting that chronic inflammatory processes with contributing high lipid values lead to earlier atherosclerosis through common immune and pathogenic mechanisms [1, 36,37]. Notably, the carriers of the ITGB3 rs5918(C) allele presented a higher PASI score when compared to non-carriers, but we cannot draw any conclusion, as it was not significant.

A large body of evidence has been presented on psoriasis and its comorbidities [1, 38]. However, how this knowledge is being translated into routine clinical practice to prevent and treat psoriasis comorbidities is still not evident [4]. Several studies have shown that patients with psoriasis and risk for CVD comorbidities are less likely to be provided cardio-protective therapy than typical patients with CVD and metabolic syndrome risk only [22, 39]. Considering this, it is crucial to screen patients, particularly of a younger age, for CVD risk with a broad panel to evaluate the potential risk factors that could contribute to higher morbidity of psoriasis patients.

In psoriatic patients, we must admit that we face a higher risk for dyslipidemia and metabolic syndrome. The risk of CVD in patients who carry ITGB3 rs5918(C) was higher but insignificant.

In various studies, as in ours, some results have not reached statistical significance, and it is then challenging to decide with certainty whether a given association of psoriasis with cardiovascular comorbidity is significant [40].

Nevertheless, such results should not be necessarily disregarded. In our opinion, these data should be thoroughly analyzed to determine their biological significance. The importance of comorbidities has to be emphasized, and awareness and effort to look for the CVD risk factors and their genetic background have to be a critical factor for dermatologists and other healthcare providers involved in the treatment and care of patients with psoriasis.

Hence, we sought to provide information on the importance of the ITGB3 rs5918C polymorphism, considering genetic inheritance in combination with environmental factors for physicians when treating psoriatic patients to improve patient care in cases with multiple comorbidities.

Conclusions

Our study found that carrying the rs5918(C) polymorphism in the ITGB3 gene presented a significantly higher prevalence of metabolic syndrome and dyslipidaemias and a higher but not significant prevalence of CVD occurrence in the patients with psoriasis. Nonetheless, we did not find a higher prevalence of the ITGB3 rs5918(C) polymorphism among psoriasis patients compared to controls.

Authors’ contributions

Conceptualization, B.D. and R.K.-P.; methodology and investigation, G.G., B.D. and G.S.; sample collection, D.G. and K.G.; clinical data D.G., G.S. and K.G; sample preparation G.G., B.D. and G.S.; data analysis and interpretation, P.T., B.D., R.K.-P. and G.S.; writing—original draft preparation, R.K.-P. and B.D.; writing—review and editing, R.K.-P. and G.S. All authors have read and agreed to the final version of the manuscript.

Data availability statement

The data that support the findings of this study are available from the corresponding author [R.K.-P.] upon reasonable request.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was conducted with the financial support the multidisciplinary project BG05M2OP001-1.002-0010-03 funded by the operative program ‘Science and education for intelligence growth’, Bulgaria and within the internal project MU-Project 15/2021 of the Medical University-Pleven, Bulgaria.