Cardioprotective effects of hesperidin on carbon monoxide poisoned in rats.

Carbon monoxide (CO) poisoning causes cardiotoxicity and so far, no definite antidote has been proposed to overcome CO-induced adverse outcomes. Hesperidin, a citrus flavonoid, has shown cardio-protective effects in cardiac ischemia/reperfusion models. This study investigated the protective effects of hesperidin against CO-induced cardiac injury. To induce CO poisoning, rats were exposed to CO at 3000 ppm for 60 min. On the exposure day and the four following days, hesperidin (at three different doses of 25, 50, and 100 mg/kg/day) was administered intraperitoneally. A group of animals received normal saline and served as the control group. The electrocardiogram (ECG) was recorded and evaluated with special focus on S-T segment changes (depression or elevation), T-wave alterations, AV block and ventricular and supraventricular arrhythmias. On day 6 (i.e., the day after the last injection day), the animals were sacrificed and the hearts were harvested and evaluated for necrosis using hematoxylin and eosin staining. In addition, Akt protein expression levels and BAX/BCL2 ratio were determined by western blotting. Our results showed that hesperidin decreased cardiac necrosis. In animals treated with hesperidin 100 mg/kg, Akt protein expression was increased, while the BAX/BCL2 ratio was significantly decreased. ECG changes were reversed in all groups 2 h following CO exposure, regardless of hesperidin administration. Overall, hesperidin decreased the deleterious cardiac effects of CO poisoning in rats.

Global skin colour prediction from DNA.

Human skin colour is highly heritable and externally visible with relevance in medical, forensic, and anthropological genetics. Although eye and hair colour can already be predicted with high accuracies from small sets of carefully selected DNA markers, knowledge about the genetic predictability of skin colour is limited. Here, we investigate the skin colour predictive value of 77 single-nucleotide polymorphisms (SNPs) from 37 genetic loci previously associated with human pigmentation using 2025 individuals from 31 global populations. We identified a minimal set of 36 highly informative skin colour predictive SNPs and developed a statistical prediction model capable of skin colour prediction on a global scale. Average cross-validated prediction accuracies expressed as area under the receiver-operating characteristic curve (AUC) ± standard deviation were 0.97 ± 0.02 for Light, 0.83 ± 0.11 for Dark, and 0.96 ± 0.03 for Dark-Black. When using a 5-category, this resulted in 0.74 ± 0.05 for Very Pale, 0.72 ± 0.03 for Pale, 0.73 ± 0.03 for Intermediate, 0.87±0.1 for Dark, and 0.97 ± 0.03 for Dark-Black. A comparative analysis in 194 independent samples from 17 populations demonstrated that our model outperformed a previously proposed 10-SNP-classifier approach with AUCs rising from 0.79 to 0.82 for White, comparable at the intermediate level of 0.63 and 0.62, respectively, and a large increase from 0.64 to 0.92 for Black. Overall, this study demonstrates that the chosen DNA markers and prediction model, particularly the 5-category level; allow skin colour predictions within and between continental regions for the first time, which will serve as a valuable resource for future applications in forensic and anthropologic genetics.

The effect of opioid dependence on conventional and novel biochemical parameters of bone metabolism.

BACKGROUND: Opioids influence bone metabolism in several ways and osteoporosis associated with the long-term use of opioids is believed to be multifactorial. OBJECTIVES: To investigate the effect of opioid dependence on conventional and novel biochemical parameters of bone metabolism. To evaluate whether the concomitant HCV infection affects these parameters. METHODS: Fifty-nine opioid-dependent subjects and 23 healthy volunteers participated in the study. Parameters of bone metabolism were determined in serum. The determined parameters were procollagen type I N-terminal propeptide (PINP), serum Beta-Crosslaps Ι (ß-CTX), total calcium (Ca), inorganic phosphorus (P), parathormone (PTH) and alkaline phosphatase bone isoenzyme (ALP). RESULTS: The results of our study show that opioid-dependent subjects exhibit higher values in those biochemical markers that are indicative of increased osteoclast activity, such as ß-CTX and ALP, compared to healthy subjects. Furthermore, in opioid-dependent subjects the values of PTH were lower, while those of PINP were higher, in comparison to healthy individuals. No significant difference in the studied parameters was found when opioid-dependent subjects positive for anti-HCV antibodies were compared with opioid-dependent subjects negative for anti-HCV antibodies. CONCLUSION: Our findings show that there is increased bone turnover (bone metabolism) in opioid-dependent subjects, compared to healthy individuals. Future research on bone mineral density in these patients will help us evaluate whether the bone remodeling process is balanced or not.

The Greek Jefferson Scale of Empathy-Medical Student Version (JSE-S): Psychometric Properties and Its Associated Factors.

The present study aimed to evaluate the psychometric properties of the Greek version of the Jefferson Scale of Empathy-Student version (JSE-S) and its association with potential predictors among Greek-speaking undergraduate medical students. This study adopted a cross-sectional, comparative-descriptive research design. The study was conducted during October and November 2023. Cronbach's α values for the JSE-S and the factors "perspective taking", "compassionate care", and "standing in the patient's shoes" showed internal consistency. The intraclass correlation coefficient for the JSE-S score in the test-retest study indicated a high level of reliability. The participants showed moderate empathy levels. Females scored higher than males in the Greek version of the JSE-S. Moreover, students enrolled in the fourth academic year showed higher empathy mean scores than those enrolled in the first year. Statistically significant empathy differences by specialty preferences or faith in God/supreme power were not found. The present study provided satisfactory evidence that the Greek JSE-S is a psychometrically sound measurement instrument. Empathy differences by gender were found in line with prior literature.

Fatal Left Ventricular Free Wall Rupture Complicating Acute Myopericarditis.

This is a case of a 59-year-old man presenting with myopericarditis. Over a 2-week period, he developed progressive symptoms and worsening pericardial effusion, leading to cardiac tamponade. Pericardiocentesis revealed hemopericardium, and multidetector computed tomography angiography showed left ventricular free wall rupture. The patient collapsed abruptly, and autopsy confirmed the findings.

Alterations in serum MMP and TIMP concentrations following chronic heroin abuse.

UNLABELLED: Abstract Context: Although opiate abuse is known to affect matrix metalloproteinases (MMPs), data on these enzymes and their tissue inhibitors in heroin addicts are scarce. OBJECTIVE: In the present study, we determined serum concentrations of MMP-2, MMP-9, tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 in heroin users, and compared them with healthy individuals. We evaluated whether 21 d of abstinence are adequate to reverse the effect of opiates and we compared seropositive with seronegative, for anti-HCV antibodies, heroin users. MATERIALS AND METHODS: Twenty-six heroin-dependent male volunteers and an equal number of healthy individuals participated in this study. ELISA was used to assess the serum levels of MMP-2, MMP-9, TIMP-1 and TIMP-2. Heroin users were assessed both upon admission and upon completion of a 21-d detoxification program. RESULTS: Serum TIMP-1 concentrations were significantly lower and the ratios MMP-2/TIMP-1, MMP-9/TIMP-1 and MMP-2/TIMP-2 were significantly higher in heroin users compared to healthy individuals. Heroin users who were seropositive had lower MMP concentrations, as well as lower MMP/TIMP ratios, compared to those who were seronegative. DISCUSSION: Our results showed that in heroin-addicted individuals, and especially those who are positive for anti-HCV antibodies, the balance between MMPs and TIMPs in serum is disrupted and this disruption cannot be restored within 21 d of abstinence. CONCLUSION: Chronic heroin abuse disrupts the balance between MMPs and TIMPs in serum and this effect is not reversible within 21 d of abstinence.

A simple HPLC method for the simultaneous determination of two selective serotonin reuptake inhibitors and two serotonin-norepinephrine reuptake inhibitors in hair, nail clippings, and cerebrospinal fluid.

A novel and simple high-performance liquid chromatography method has been developed for the simultaneous determination of two selective serotonin reuptake inhibitors (fluoxetine and paroxetine) and two serotonin-norepinephrine reuptake inhibitors (venlafaxine and duloxetine) in alternative samples of toxicological interest such as hair, nail clippings, and cerebrospinal fluid (CSF). The separation was achieved on a Hichrom Kromasil 100-5C(18) (250 × 4.6 mm) 5 µm column by using ammonium acetate (0.05 M)-acetonitrile (59:41% v/v) as the mobile phase, delivered isocratically at a flow rate of 1.3 mL/min, within ca. 10 min. Ultraviolet detection at 235 nm was used for monitoring the eluting analytes. Validation was performed in terms of linearity, selectivity, accuracy, precision, and stability. Correlation coefficients were greater than 0.9954. The limits of quantitation ranged between 0.3 and 2.1 ng/µL for all analytes in the liquid matrix (CSF), while the respective values were in the range of 0.3-3.6 ng/mg for solid matrices (hair and nail clippings), with an injection volume of 20 µL. Repeatability and intermediate precision (relative standard deviation, RSD%) were less than 16.6%. The method was successfully applied to actual hair and nail samples from a patient under fluoxetine treatment.

The frequency of ethanol, higher alcohols and other low molecular weight volatiles in postmortem blood samples from unnatural deaths.

The determination of various volatiles in postmortem blood samples has been reported in many previous studies. The presence of some of them in postmortem specimens reflects microbial activity in the sample while others are detected mainly after consumption of alcoholic beverages or due to antemortem metabolic processes. This contribution aims to determine in 1954 postmortem blood samples, from respective number of unnatural deaths autopsy cases, the frequency of detection of some common volatile compounds, including acetaldehyde, acetone, 2-propanol, ethyl acetate, methanol, as well as, the higher alcohols 1-propanol, 1-butanol, isobutanol and 2-methyl-1-butanol and 3-methyl-1-butanol; moreover, their patterns in respect to the ethanol and 1-propanol concentrations and the putrefaction state of the corpse at autopsy. Acetone was the most frequently detected volatile (82 %), followed by acetaldehyde (44 %) and 2-propanol (34 %). Methanol was detected in 12 % of the samples and only in the presence of ethanol. The most frequently detected higher alcohol was 1-propanol (51 %), followed by isobutanol (8.5 %), 1-butanol (3.6 %) and methyl-butanols (2.0%); the latter three higher alcohols were detected in the presence of 1-propanol indicating possibly a common origin. Samples from cases with putrefaction had higher 1-propanol concentrations, than those without putrefaction, and, moreover, they were significantly correlated with 1-butanol concentrations.

Contributing factors common to COVID­19 and gastrointestinal cancer.

The devastating complications of coronavirus disease 2019 (COVID­19) result from the dysfunctional immune response of an individual following the initial severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) infection. Multiple toxic stressors and behaviors contribute to underlying immune system dysfunction. SARS­CoV­2 exploits the dysfunctional immune system to trigger a chain of events, ultimately leading to COVID­19. The authors have previously identified a number of contributing factors (CFs) common to myriad chronic diseases. Based on these observations, it was hypothesized that there may be a significant overlap between CFs associated with COVID­19 and gastrointestinal cancer (GIC). Thus, in the present study, a streamlined dot­product approach was used initially to identify potential CFs that affect COVID­19 and GIC directly (i.e., the simultaneous occurrence of CFs and disease in the same article). The nascent character of the COVID­19 core literature (~1­year­old) did not allow sufficient time for the direct effects of numerous CFs on COVID­19 to emerge from laboratory experiments and epidemiological studies. Therefore, a literature­related discovery approach was used to augment the COVID­19 core literature­based 'direct impact' CFs with discovery­based 'indirect impact' CFs [CFs were identified in the non­COVID­19 biomedical literature that had the same biomarker impact pattern (e.g., hyperinflammation, hypercoagulation, hypoxia, etc.) as was shown in the COVID­19 literature]. Approximately 2,250 candidate direct impact CFs in common between GIC and COVID­19 were identified, albeit some being variants of the same concept. As commonality proof of concept, 75 potential CFs that appeared promising were selected, and 63 overlapping COVID­19/GIC potential/candidate CFs were validated with biological plausibility. In total, 42 of the 63 were overlapping direct impact COVID­19/GIC CFs, and the remaining 21 were candidate GIC CFs that overlapped with indirect impact COVID­19 CFs. On the whole, the present study demonstrates that COVID­19 and GIC share a number of common risk/CFs, including behaviors and toxic exposures, that impair immune function. A key component of immune system health is the removal of those factors that contribute to immune system dysfunction in the first place. This requires a paradigm shift from traditional Western medicine, which often focuses on treatment, rather than prevention.

Development and validation of a direct headspace GC-FID method for the determination of sevoflurane, desflurane and other volatile compounds of forensic interest in biological fluids: application on clinical and post-mortem samples.

A simple and reliable headspace GC-flame ionization detection (HS-GC-FID) method has been developed and validated for the simultaneous determination of seven volatile compounds of forensic interest: sevoflurane, desflurane, ethanol, methanol, 1-propanol, acetone and acetaldehyde. All seven compounds including acetonitrile (internal standard) eluted within 10 min and were well resolved with no endogenous interference. Good linearity was observed in the range of 1-12 mg/dL for both anesthetics and 2.5-40 mg/dL for the other five analytes. The method showed good precision, sensitivity and repeatability. Most of the analytes remained stable during the storage of samples at 4°C. Desflurane and acetone degraded (>10%), when the samples remained on the autosampler for more than 2 and 3 h, respectively. The method was finally applied on clinical and post-mortem blood and urine samples. The clinical samples were collected both from patients who underwent surgery, as well as from the occupationally exposed medical and nursing staff of the university hospital, working in the operating rooms. The hospital staff samples were found negative for all compounds, while the patients' samples were found positive for the anesthetic administered to the patient. The post-mortem blood samples were found positive for ethanol and acetaldehyde.

Disposable pipette extraction for gas chromatographic determination of codeine, morphine, and 6-monoacetylmorphine in vitreous humor.

The availability of a sensitive and rapid analytical method for the determination of opiates, and other substances of forensic interest, in a variety of biological specimens is of utmost importance to forensic laboratories. Solid-phase extraction is very popular in the pre-treatment of forensic samples. Nevertheless, a new approach, disposable pipette extraction (DPX), is gaining increasing interest in sample preparation. DPX has already been applied to the analysis of drugs of abuse in common biological matrices, such as urine and blood, but has not yet been evaluated on alternative biological samples, such as vitreous humor. The objective of this study was to evaluate the applicability of DPX on the analysis of opiates in vitreous humor. The currently developed method is fast, reliable, and easy to perform. The sensitivity, precision, and accuracy are satisfactory. Recoveries obtained are within the range of 72-91%, whereas the sample volume of vitreous humor required is only 100 µL.

Epigenetic mechanisms in metal toxicity.

The true understanding of epigenetics evolved over time as our knowledge on DNA methylation and chromatin modifications and their effects on gene expression increased. The current flurry of research on epigenetics and the increasing documentation of the effects of various environmental factors on DNA methylation, chromatin modification, as well as on the expression of small non-coding RNAs (ncRNAs) have expanded the scope of research on the etiology of various diseases including cancer. The current review briefly discusses various molecular mechanisms of epigenetic regulation of gene expression, and expands the discussion with examples of heavy metal-induced alterations of gene expression and the associated epigenetic changes.

Global DNA methylation levels in white blood cells of patients with chronic heroin use disorder. A prospective study.

BACKGROUND: Increasing scientific evidence shows the significant role of epigenetic mechanisms in drug use disorder, abstinence and relapse. Studies on human subjects are limited compared to those on animals, for various reasons such as poly-substance abuse, high drop-out rate and technical difficulties. OBJECTIVES: Our goal was to evaluate whether a monitored abstinence period of 21 days could induce changes in global DNA methylation in chronic heroin users. METHOD: In the current study, we present data on global DNA methylation on a set of 18 male patients with chronic heroin use disorder, carefully selected based on inclusion and exclusion criteria, who were hospitalized and closely monitored during a 21-day detoxification program, one of the few where no opioid agonist is administered. The participants were sampled twice, once upon enrolment to the program and once upon completion. RESULTS: According to our results, no difference in global DNA methylation was detected between samples collected upon enrolment and samples collected upon completion of the program. CONCLUSION: The findings of this study do not rule out the possibility that the 21-day abstinence period was not long enough to observe changes in global DNA methylation, or that abstinence induced site-specific methylation changes (but not global changes), that certainly merit further evaluation.

Common contributing factors to COVID-19 and inflammatory bowel disease.

The devastating complications of coronavirus disease 2019 (COVID-19) result from an individual's dysfunctional immune response following the initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Multiple toxic stressors and behaviors contribute to underlying immune system dysfunction. SARS-CoV-2 exploits the dysfunctional immune system to trigger a chain of events ultimately leading to COVID-19. We have previously identified many contributing factors (CFs) (representing toxic exposure, lifestyle factors and psychosocial stressors) common to myriad chronic diseases. We hypothesized significant overlap between CFs associated with COVID-19 and inflammatory bowel disease (IBD), because of the strong role immune dysfunction plays in each disease. A streamlined dot-product approach was used to identify potential CFs to COVID-19 and IBD. Of the fifty CFs to COVID-19 that were validated for demonstration purposes, approximately half had direct impact on COVID-19 (the CF and COVID-19 were mentioned in the same record; i.e., CF---→COVID-19), and the other half had indirect impact. The nascent character of the COVID-19 core literature (∼ one year old) did not allow sufficient time for the direct impacts of many CFs on COVID-19 to be identified. Therefore, an immune system dysfunction (ID) literature directly related to the COVID-19 core literature was used to augment the COVID-19 core literature and provide the remaining CFs that impacted COVID-19 indirectly (i.e., CF---→immune system dysfunction---→COVID-19). Approximately 13000 potential CFs for myriad diseases (obtained from government and university toxic substance lists) served as the starting point for the dot-product identification process. These phrases were intersected (dot-product) with phrases extracted from a PubMed-derived IBD core literature, a nascent COVID-19 core literature, and the COVID-19-related immune system dysfunction (ID) core literature to identify common ID/COVID-19 and IBD CFs. Approximately 3000 potential CFs common to both ID and IBD, almost 2300 potential CFs common to ID and COVID-19, and over 1900 potential CFs common to IBD and COVID-19 were identified. As proof of concept, we validated fifty of these ∼3000 overlapping ID/IBD candidate CFs with biologic plausibility. We further validated 24 of the fifty as common CFs in the IBD and nascent COVID-19 core literatures. This significant finding demonstrated that the CFs indirectly related to COVID-19 -- identified with use of the immune system dysfunction literature -- are strong candidates to emerge eventually as CFs directly related to COVID-19. As discussed in the main text, many more CFs common to all these core literatures could be identified and validated. ID and IBD share many common risk/contributing factors, including behaviors and toxic exposures that impair immune function. A key component to immune system health is removal of those factors that contribute to immune system dysfunction in the first place. This requires a paradigm shift from traditional Western medicine, which often focuses on treatment, rather than prevention.

Exposure to cadmium and copper triggers cytotoxic effects and epigenetic changes in human colorectal carcinoma HT-29 cells.

Recent scientific evidence suggests a link between epigenetic changes (DNA methylation) and tumorigenesis. Moreover, a potential carcinogenic mechanism of cadmium was associated with changes in DNA methylation. In this study we investigated the impact of CdCl2 and CuSO4 aqueous solutions on DNA methylation in HT-29 cells by quantifying DNA methyltransferase (DNMT1, DNMT3A and DNMT3B) mRNA expression. Furthermore, we also studied the cytotoxic and anti-migratory potential of these substances. The results showed a dose-dependent decrease of viable cell percentage following 24 h of exposure (at concentrations of 0.05; 0.2; 1; 10 and 100 µg/ml), and an inhibitory effect on HT-29 cell migration capacity. In addition, RT-qPCR results showed that cadmium acts as a hypomethylating agent by suppressing DNMT expression, whereas copper acts as a hypermethylating compound by increasing DNMT expression. These findings suggest a cytotoxic potential of both cadmium and copper on HT-29 cells and their capacity to induce epigenetic changes.

Isoprostane as a marker of oxidative stress in chronic heroin users: correlation with duration of heroin use or concomitant hepatitis C infection.

BACKGROUND: Although chronic heroin abuse has been extensively linked to oxidative stress, and while plasma 15-F(2t)-IsoP is considered a good indicator of oxidative stress, there remain few references in the literature about the plasma concentration of this marker in heroin dependent subjects. OBJECTIVES: To determine plasma 15-F(2t)-IsoP, as a marker of oxidative stress, in chronic heroin users, and to examine whether the values of this marker correlate with the duration of heroin use or with the presence of anti-HCV antibodies. METHODS: Forty-two chronic heroin users and twenty two healthy control subjects were recruited for this study. An enzyme-immunoassay method was used for the determination of 15-F(2t)-IsoP in plasma. RESULTS: Plasma 15-F(2t)-IsoP values were significantly higher in chronic heroin users compared to healthy controls. No correlation was found between the values of plasma 15-F(2t)-IsoP and the duration of heroin use. Heroin dependent subjects positive for anti-HCV antibodies had significantly lower values of plasma 15-F(2t)-IsoP as compared to those without a history of HCV infection. CONCLUSIONS: The elevated plasma 15-F(2t)-IsoP values in heroin dependent subjects, compared to healthy individuals, indicate a shift of the balance between oxidants and antioxidants towards the former and suggest that heroin dependent subjects could benefit from an antioxidant therapy.

Evaluation of prooxidant-antioxidant balance in chronic heroin users in a single assay: an identification criterion for antioxidant supplementation.

BACKGROUND: Opiate abuse has been linked to oxidative stress, through the separate evaluation of oxidants and antioxidants. OBJECTIVES: To determine prooxidant-antioxidant balance (PAB) in chronic heroin users in a single assay, easily applied in a clinical setting. Specifically, to examine whether PAB values correlate with the duration of abuse or with the presence of anti-HCV antibodies. METHODS: Sixty-four chronic heroin users - 34 cases and 30 controls - participated in this study. PAB was determined by an Enzyme-linked immunosorbent assay (ELISA) method, developed by members of the study group. RESULTS: In heroin users, oxidative balance was disrupted in favor of prooxidants. There was no correlation of PAB values with the duration of abuse or with the presence of anti-Hepatitis C virus (HCV) antibodies. CONCLUSIONS: Chronic heroin users can benefit from an antioxidant therapy, and the method currently presented can be used as an identification criterion.

The role of MiRNA-21 in gliomas: Hope for a novel therapeutic intervention?

Gliomas are the most common primary brain tumors in adults. They are generally very resistant to treatment and are therefore associated with negative outcomes. MicroRNAs (miRNAs) are small, non-coding RNA molecules that affect many cellular processes by regulating gene expression and, post-transcriptionally, the translation of mRNAs. MiRNA-21 has been consistently shown to be upregulated in glioma and research has shown that it is involved in a wide variety of biological pathways, promoting tumor cell survival and invasiveness. Furthermore, it has been implicated in resistance to treatment, both against chemotherapy and radiotherapy. In this review, we gathered the existent data on miRNA-21 and gliomas, in terms of its expression levels, association with grade and prognosis, the pathways it involves and its targets in glioma, and finally how it leads to treatment resistance. Furthermore, we discuss how this knowledge could be applied in clinical practice in the years to come. To our knowledge, this is the first review to assess in extent and depth the role of miRNA-21 in gliomas.

Impact of vitamin D receptor gene polymorphisms on vitiligo susceptibility and clinical features in a Southeastern European Caucasian population.

An association of vitamin D receptor (VDR) polymorphisms and vitiligo has been suggested. However, previous studies have reported contradictory results while including limited data among Caucasians. The aim of this single­center study was to evaluate the effect of three common VDR gene polymorphisms (FokI, TaqI and BsmI) on susceptibility and clinical aspects of vitiligo in a Southeastern European Caucasian population. A total of 110 unrelated vitiligo cases and 509 general population controls were enrolled from October 2018 to November 2019. Genomic DNA was extracted from whole blood after de­identification and anonymization of the samples and genotyped for the selected VDR polymorphisms by the qPCR (melting curve analysis). Subgroup analysis by clinical features among subsets of patients indicated that, compared to subjects with the FokI TT genotype or T allele, carriers of the FokI CC genotype or C allele exhibited significantly decreased risk of developing vitiligo before the age of 30 [TT vs. CC: odds ratio (OR)=0.286, 95% confidence interval (CI): 0.083­0.984, P=0.041; T vs. C: OR=0.545, 95% CI: 0.313­0.948, P=0.031]. Intra­patient analysis also revealed that, compared to T allele, the presence of TaqI C allele was adversely associated with the incidence of concurrent leukotrichia (T vs. C: OR=1.874, 95% CI: 1.018­3.451, P=0.042). Comparisons between the case and control groups showed no evidence to support an association between susceptibility to vitiligo and the VDR BsmI, TaqI, and FokI polymorphisms in this cohort. Thus, the studied VDR polymorphisms might indirectly impact the clinical course and treatment decision­making despite their lack of association with vitiligo per se. Further research with larger sample sizes, especially across Caucasian individuals, should be performed to confirm these findings.