Study of serum level of kisspeptin and interferon-beta in genital wart patients.

Background: Researchers are interested in genital wart (GW) studies due to their increased incidence. In a single experimental research, virally infected mouse models showed elevated kisspeptin levels and low interferon levels. Objective: The objective of the study was to evaluate the serum levels of kisspeptin and interferon (INF)-beta in GW patients. Patients and Methods: Forty patients with GWs and forty healthy participants of comparable age and sex as a control group were included in this case-control study. Serum levels of kisspeptin and IFN-beta were measured using ELISA during the period from December 2021 to April 2022. Results: Kisspeptin was significantly higher among cases than controls, whereas IFN-beta level was lower among cases than controls (P < 0.001). There were no significant relations between kisspeptin and IFN-beta levels and the clinical data for the studied participants, and there was no significant correlation between both (P > 0.05). Conclusion: The reported increased kisspeptin level which was associated with decreased interferon-beta level in patients with GWs might indicate a new insight into viral infection pathogenesis. Further research including all steps in kisspeptin/G protein-coupled receptor 54 pathway is required. Targeted therapy for this pathway may be of value for those patients.

Assessment of cytochrome P450 1A1 gene polymorphism and vitamin A serum level in psoriasis vulgaris.

Psoriasis is characterized by cutaneous hyperproliferation, secondary to immune system dysregulation. Vitamin A regulates the immune response and sustains epithelial tissue hemostasis. The CYP1A1 gene, has many biological actions, including vitamin A metabolism. To evaluate CYP1A1 gene polymorphism and serum vitamin A level in patients with psoriasis vulgaris, a case-control study involving two groups was conducted: group 1 (45 patients with psoriasis vulgaris) served as the cased group and group 2 (45 healthy participants who were sex and age matched) acted as the control group. CYP1A1 (rs1048943) gene polymorphism and vitamin A serum level were assessed by TaqMan allelic discrimination (PCR) and ELISA, respectively. AG genotype was present only in cases (22.2%), while AA genotype was present in all controls (P=.001). Vitamin A levels were lower in cases than in controls (32.0 ± 7.41 vs. 46.2 ± 15.7 µg/ml, respectively) (P<.001). AG genotype was associated with a lower vitamin A level (P=.001). The detected genotype difference between psoriasis patients and controls, which was associated with a lower serum vitamin A level and was also lower in more severe cases, suggests a role of the CYP1A1 gene and vitamin A in disease pathogenesis and prognosis.

Mitochondrial DNA copy number as a diagnostic marker and indicator of degree of severity in alopecia areata.

Alopecia areata (AA) is a disorder with several etiologies. The evidence suggests that the absolute copy number of mitochondrial deoxyribonucleic acid (mtDNA), as well as proportion of mutated mtDNA copies, determines disease onset. This study aims to quantify the relative index of the mtDNA copy number in patients with AA and healthy controls and correlate the results with the existing clinical information. This case-control study included 50 patients with AA and 50 age- and sex-coordinated healthy persons as controls. The severity of AA was weighed using the Severity of Alopecia Tool and Kavak's classification. The relative index of the mtDNA copy number was measured by real-time qPCR. Significant statistical difference was observed between cases and controls regarding mean mtDNA copy number, p < .001. There was significant positive correlation with SALT score (p = â€…0.001). A cutoff value of >1.619 N/µL could significantly diagnose AA cases (p < .001), and a cutoff value of > 1.36 N/µL could discriminate mild AA cases from those with moderate AA (p = â€…0.007). The relative index of mtDNA copy number is significantly elevated in AA cases and could be helpful in diagnosing and evaluating AA severity.

CD93 has a crucial role in pathogenesis of psoriasis.

BACKGROUND: Psoriasis is a chronic, immune-related disorder; inflammation, higher rate of epidermal proliferation, and angiogenesis are the main pathognomonic features. Cluster of differentiation 93 (CD93), an angiogenic element, plays a role in cell adhesion regulation and has a putative function in inflammation. OBJECTIVE: To assess CD93 immunohistochemical expression in psoriatic skin and the association of CD93 single nucleotide polymorphisms (SNPs) rs2749817 to disease pathogenesis and severity. METHODS: This case-control study was done on 50 patients with psoriasis vulgaris beside 50 age- and sex-matched healthy controls. Assessment of psoriasis severity was done by Psoriasis Area and Severity Index (PASI) score. 3 mm punch skin biopsies were taken from every participant, and hematoxylin and eosin staining and immunohistochemical staining for CD93 antibody were done. Assessment of CD93 rs2749817 gene polymorphism by the TaqMan allelic discrimination assay technique (real-time PCR) was done. RESULTS: Immunohistochemical expression of CD93 showed membrano-cytoplasmic localization in both endothelial and inflammatory cells of cases and controls with significant more positivity in dermal endothelial and inflammatory cells of cases than controls (p = 0.001 and 0.014 respectively). Strong intensity was present in 18 of cases endothelial cells and 24 inflammatory cells with absence in controls (p =  0.001 for both) with significantly higher H-score and higher percent of positive cells (p  =  0.001 for both). The TC genotype was lower in patients compared to control (p-value = 0.006) and CC genotype which was present only in cases (p-value = 0.021). CONCLUSION: Cluster of differentiation 93 has an essential role in psoriasis and an encouraging future therapy for psoriasis.

Interleukin19 gene polymorphism and its serum level in acne vulgaris patients.

Numerous cytokines are involved in acne vulgaris pathogenesis, though few studies correlate interleukin IL-19 to acne vulgaris. So this study aimed to assess the IL-19 (rs 2243191) gene polymorphism and its serum level in acne vulgaris. This case-control study involved 90 acne vulgaris cases and 90 age- and sex-matched controls. Acne severity was assessed according to Global Acne Grading System (GAGS), and serum IL-19 was assessed by ELISA and IL-19 (rs 2243191) gene polymorphism was assessed by real time PCR. This study showed that acne cases had significantly higher IL-19 levels than controls. Also, its level was significantly higher in severe cases than moderate and mild cases. Regarding IL-19 gene polymorphism (rs 2243191), TT and CT genotypes were significantly higher in patients than in controls. The incidence of minor allele T was greater in patients than in controls. There were significant differences between IL-19 genotypes and disease severity. Serum IL-19 was significantly higher in genotypes TT and CT acne cases than in those with genotype CC. We concluded that TT genotype of IL-19 might be a hereditary risk factor for acne vulgaris development. It is associated with a high IL-19 serum level, which could be a marker of acne severity...

Circulating long noncoding RNA growth arrest-specific transcript 5 as a diagnostic marker and indicator of degree of severity in plaque psoriasis.

BACKGROUND: The current study aims at evaluating the role of circulating or cell-free long noncoding ribonucleic acid (lncRNA) growth arrest-specific 5 (GAS5) in plaque psoriasis and at investigating its relationship with the presented clinical data. METHODS: This case-control study was conducted on 180 subjects, divided into two main categories as follows: 90 cases with plaque psoriasis and 90 age- and sex-matched healthy controls. Full history taking, thorough general examination, and full dermatological examination with determination of number and site of lesions were performed. Disease severity was assessed by Psoriasis Area Severity Index (PASI) score. Relative quantification of the expression level of cell-free lncRNA (GAS5) was performed using real-time polymerase chain reaction (RT-PCR) technique. RESULTS: There was significant increase of GAS5 expression level in cases when compared with controls (U = 719.0, P < 0.001). Indeed, there was significant positive correlation between GAS5 and PASI score (r = 0.0.668, P < 0.001). Receiver operating characteristic (ROC) curve showed that GAS5 could identify patients from controls: GAS5 at a cut-off value ≥0.31 provides a sensitivity of 95.56% and a specificity of 82.22%; at a cut-off value ≥0.75, it can differentiate between mild and moderate cases, at a sensitivity of 77.78% and a specificity of 91.43%; at a cut-off value ≥1.61, it can discriminate between moderate and severe cases, with a sensitivity of 71.43% and a specificity of 74.07%. CONCLUSION: lncRNA GAS5 expression could be considered as a diagnostic marker of plaque psoriasis and indicator of its severity.

Genetic polymorphism of liver X receptor gene in vitiligo: Does it have an association?

BACKGROUND: Vitiligo is an acquired depigmentation of the skin and the mucous membranes, exhibited as white macules and patches due to selective loss of melanocytes. Etiological theories of vitiligo include genetic, immunological, neurohormonal, cytotoxic, biochemical, oxidative stress, and newer theories of melanocytorrhagy and diminished melanocytes survival. It has been revealed that liver X receptor alpha gene is expressed in skin tissue such as sebaceous glands, hair follicle, keratinocytes, and fibroblasts and is linked to various skin disorders as acne vulgaris and psoriasis. AIM OF THE STUDY: To evaluate the association between liver X receptor-α gene polymorphism (rs11039155 and rs2279238) and vitiligo and whether they are related to disease activity and severity or not. SUBJECTS AND METHODS: 50 vitiligo patients and 20 age- and sex-matched apparently healthy controls were enrolled. All the included subjects were genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis technique for (-6G/A) and (+1257C/T) SNPs. RESULTS: Significant statistical difference between cases and controls regarding genotype and allele frequencies for -6G/A polymorphism with predominance of AA genotype (OR: 5.1, 95% CI: 1.6-15.9) and A allele (OR: 5.3, 95% CI: 1.6-15.9) in cases and also for +1257C/T polymorphism with predominance of TT genotype OR: 9.2 (95% CI: 1.4-82.9) and T allele OR: 3.4 (95% CI: 1.4-8.1) in vitiligo cases. No significant relationship between -6G/A genotypes nor +1257C/T genotypes and disease activity and severity. CONCLUSION: The study showed significant association between Liver X receptor gene polymorphisms (-6G/A, +1257 C/T) and development of vitiligo in Egyptian patients. However, it failed to show any relation with disease activity nor severity.

Neuronal Precursor Cell Expressed Developmentally Down Regulated 4 (NEDD4) Gene Polymorphism Contributes to Keloid Development in Egyptian Population.

BACKGROUND: Keloids represent chronic fibroproliferative skin disorders in which there is deposition of extracellular components, especially type 1 collagen, fibronectin and elastin, in excessive amounts. NEDD4 is associated with fibrosis found in abnormal wound healing through increased fibroblast proliferation and regulation of type 1 collagen expression. The exact etiology of keloid formation is undefined, but the role of genetic factors was demonstrated. OBJECTIVE: To investigate the polymorphism of the NEDD4 gene rs8032158 in a sample of Egyptian patients who have keloids. METHODS: The current case-control study was conducted in 160 unrelated subjects; 100 keloid patients and 60 ages and sex coincided with apparently healthy controls. All subjects underwent a complete history, and weight and length were measured to calculate body mass index (BMI). The Vancouver Scar Scale (VSS) was used to assess keloid severity. An analysis of the polymorphism of the NEDD4 gene rs8032158 T/C was performed using taqman allelic discrimination (real-time PCR). RESULTS: The rs8032158 CC genotype was observed significantly in keloid patients and increased the risk of keloid development by approximately 2 times (p = 0.003, OR = 1.80). The C allele significantly increased the risk of keloid development by approximately 2 times (P = 0.002, OR = 2.08). The carriers of the CC genotype were significantly associated with severe keloid form and with the highest VSS values. CONCLUSION: The polymorphism of the NEDD4 gene rs8032158 could participate in the formation of keloids in the Egyptian population. The NEDD4 rs8032158 CC genotype may have a role in keloid severity.

Relationship Between sCD163 and mCD163 and Their Implication in the Detection and Typing of Leprosy.

BACKGROUND: Leprosy is a chronic contagious disease caused by Mycobacterium lepraea. CD163 is a monocyte trans-membrane glycoprotein receptor (mCD163) that sheds from the cell surface and circulates as a soluble (serum) form (sCD163). Changes in the mCD163 and sCD163 levels could mirror the categorization of inflammatory procedure, demonstrating a possible use of CD163 as a diagnostic indicator of inflammation. OBJECTIVE: To investigate the possible role of CD163 (sCD163 and mCD163) in leprosy pathogenesis and to assess whether CD163 is a helpful inflammatory marker of leprosy development and typing. PATIENTS AND METHODS: This case control study included 70 leprosy patients and 30 healthy controls. Leprosy patients were classified according to the Madrid criteria (1953) into: tuberculoid leprosy (TT), border-line leprosy (BL), and lepromatous leprosy (LL). For all participants, complete blood count (CBC), serum CD163 using ELISA and monocytes positive for CD163 using flow cytometry were done. RESULTS: Leprosy patients had significantly low WBCs and platelet counts (p<0.001) and had significantly higher sCD163 (p=0.025) and mCD163 (p=0.042) that were highest in LL followed by BL, then TT patients (p<0.001). There was a significant positive correlation between mCD163 and sCD163 levels in leprosy patients (r=0.896, p<0.001). ROC analysis revealed a significant role of serum sCD163 and of mCD163 positive monocytes in the detection (p<0.001) and typing of leprosy (p=0.002 and p<0.001, respectively). CONCLUSION: Both sCD163 and mCD163 positive monocytes may have an active role in leprosy pathogenesis. They could be potential biomarkers for leprosy detection and typing.

Protein tyrosine phosphatase nonreceptor type 22 gene polymorphism in alopecia areata: Does it have an association with disease severity?

BACKGROUND: Alopecia areata is a condition involving hair loss from certain or all areas of the body. It has been considered as an immune-mediated disease, characterized by the infiltration of CD4+ and CD8+ lymphocytes in the hair follicles. AIM OF THE STUDY: The study aimed to assess whether protein tyrosine phosphatase nonreceptor type 22 gene single nucleotide polymorphism 1858C/T has any relationship with alopecia areata in Egyptian patients and whether it is associated with disease severity or not. SUBJECTS AND METHODS: Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) C1858T gene polymorphism was identified using polymerase chain reaction-restriction fragment length polymorphism analysis technique in 60 patients suffering from alopecia areata and 30 age- and sex-matched healthy controls. Disease severity was assessed using SALT score. RESULTS: CT and TT genotypes were significantly higher in the patients' group (P = .005), OR = 4.38 95% CI [1.48-12.96], with significant statistical predominance of T allele in patients, P = .003, OR = 3.86, 95% CI [1.52-9.77]. There was also a positive significant relationship between protein tyrosine phosphatase nonreceptor type 22 genotype CT and SALT score. CONCLUSION: PTPN22 1858T allele is associated with the development and severity of alopecia areata in Egyptians.

Resistin adipokin in atopic dermatitis patients: A clinical, biochemical, and genetic study.

BACKGROUND/OBJECTIVES: Atopic dermatitis (AD) is an inflammatory chronic skin disorder. The etiology of AD is not fully understood. Therefore, we aimed by this study to shed light on the potential role of resistin in an etiopathogenesis of AD through investigation of resistin rs3745367 single nucleotide polymorphism (SNP) and resistin serum levels, and their relation to leukocytic count in a sample of Egyptian patients having atopic dermatitis. METHODS: This case-control study included 45 patients having AD and 40 controls. SCORAD index was assessed to evaluate the severity of AD. CBC, ELISA, and PCR-RFLP were performed to detect leukocytic count, resistin serum level, and resistin rs3745367 SNP, respectively. RESULTS: Atopic dermatitis patients had significant low serum resistin concentrations (P = .036) and a significantly high frequency of leukocytosis (P = .003). Low resistin serum levels were significantly related to AD disease severity (P < .001) and the presence of leukocytosis (P < .001). Resistin rs3745367 GG genotype (P = .030), as well as its G allele (P = .019), was expressively associated with AD development, and both increased the risk of AD by 3- and 2-fold, respectively. Resistin rs3745367 GG genotype was significantly linked to low resistin serum levels (P < .001), AD-positive family history (P = .015), and the presence of leukocytosis (P < .001). CONCLUSIONS: Resistin rs3745367 gene polymorphism may contribute to the development of AD. Resistin may have an immune-modulating active character in the AD etiopathogenesis that could be mediated through its anti-inflammatory effect. From this piece of work, we may suggest resistin as a new therapy to mitigate the pro-inflammatory environment found in AD.

Interleukin-6 serum level and gene polymorphism in keloid patients.

The formation of keloid is associated with accumulation of extracellular matrix (ECM) formed mainly of collagen and fibronectin. Persistent deregulated IL-6 synthesis causes the development of various diseases. This study aim to investigate interleukin 6 (IL-6) serum level and gene polymorphism in a sample of Egyptian patients having keloid. This study was carried out on 90 subjects; 60 patients with keloid, and 30 age and sex matched apparently healthy control. All subjects underwent full history taking, clinical examinations, weight and length measuring to calculate BMI, dermatological examination, analysis of IL6-572 gene polymorphism using REFLP- PCR and IL-6 serum level using ELISA.IL-6 serum levels were significantly higher in keloid patients than control group (75.54±39.18) vs (19.17±6.06), (p <0.001). The higher serum levels of IL-6 were associated with GG genotype (104.84±19.12) followed by CG (57.64±35.38) genotype (P<0.001). GG genotype was significantly higher in keloid patients and increased the risk for keloid development by nearly14 folds (p<0.001, OR (95%CI) =13.81).  CG genotype was significantly observed in keloid patients and increased the risk for keloid development by about 4 times (p=0.010, OR (95%CI) =4.27). G Allele significantly increased the risk for keloid development by about 5 folds (P <0.001 OR =5.11). In conclusion, there was a great association between IL-6 572 gene polymorphism and its serum level in patients with keloid specifically who have family history.

Role of 11ß HSD 1, rs12086634, and rs846910 single-nucleotide polymorphisms in metabolic-related skin diseases: a clinical, biochemical, and genetic study.

BACKGROUND: 11ß HSD1 generates cortisol from cortisone. 11ß HSD1 single-nucleotide polymorphism (SNP) was associated with metabolic syndrome (MeTS). Although the relation of acne vulgaris (AV) and skin tags (STs) with MeTS has been reported, the relationship between 11ß HSD 1 SNP and cortisol activity in those patients has not studied till now. AIMS: To investigate, two 11ß-HSD1 SNPs (rs846910 and rs12086634), serum lipid profile and cortisol levels in patients with AV and STs in an Egyptian population. PATIENTS AND METHODS: This case-control study was performed on 50 patients having STs and 50 complaining of AV and 50 sex- and age-matched controls. We searched for serum lipid profile, cortisol levels, and 11ß-HSD1 rs846910 and rs12086634 SNPs using real time-PCR. RESULTS: Compared to controls,11ß-HSD1 rs846910 GA genotype carriers had significantly higher risks for developing AV and STs by 3.4- and 4.9-fold, respectively, and its A allele increases these risks by 3.1 and 4.4 times, respectively. Also, 11ß-HSD1 rs12086634 TG genotype increases the risk of AV by 3.2-fold, as well as STs by 3.5-fold, and its G allele increases the risk of AV by 3.2-fold and STs by 7-fold. In AV and ST patients, rs846910 GA genotype demonstrated significant associations with elevated body mass index (BMI), and cholesterol, low density lipoprotein (LDL), cortisol, and decreased high density lipoprotein serum levels, respectively. However, rs12086634 GG genotype was significantly associated with increased BMI, cholesterol, and LDL serum levels in patients with AV and STs, in addition to the number of STs and serum cortisol levels in ST patients. CONCLUSION: 11ß-HSD1 rs846910 and rs12086634 gene polymorphisms may contribute to AV and STs pathogenesis, that may be mediated through enhancing the enzymatic activity (increasing cortisol levels). AV and STs are associated with obesity and atherogenic lipid profile. Diagnosis of AV and STs may play a role in early detection of the MeTS.