Study on the polymorphism of TNFα-238G/A and -308G/A gene in patients with alopecia areata

目的:探讨肿瘤坏死因子(TNF)-α的-238G/A和-308G/A基因多态性与斑秃的关系.方法:运用多聚酶链反应技术检测102例斑秃及141例正常人TNF-α的-238G/A和-308G/A基因多态性.结果:斑秃组-238 G/G、G/A和A/A基因型频率分别为0.9510、0.490和0,对照组分别为0.9574、0.0426和0;斑秃组-238G和-238A基因频率分别为0.9755和0.0245,对照组分别为0.9787和0.0213.-238G/A各种基因型频率在患者组与正常对照组之间的差异无统计学意义(P > 0.05).斑秃组-308G/G、G/A和A/A基因型频率分别为0.9118、0.0784和0.0098,对照组分别为0.9277、0.0567和0.0213;斑秃组-308G和-308A基因频率分别为0.9510和0.0490,对照组分别为0.9504和0.0496.斑秃组TNF-α-238G/A和-308G/A两位点单体型分析结果表明,这两个位点组成的单体型不存在过度传递.结论:TNF-α的-238G/A和-308G/A基因多态性与斑秃可能没有相关性.     

Genetic association of IFN-γ +874T/A polymorphism in Mexican patients with drug-induced Stevens-Johnson syndrome/toxic epidermal necrolysis

Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are rare, but potentially life-threatening diseases, characterized by widespread epidermal necrosis and are predominantly drug induced. There is a paucity of data regarding the role of cytokine and cytokine receptors polymorphisms in the pathoimmunology of SJS/TEN. The aim of this study was to investigate the role of TNF-α-308, IFN-γ +874, IL-10-1082, IL-13 Arg130Gln, and IL-4R Gln551Arg gene polymorphisms in SJS/TEN in Mexican Mestizo patients. Twenty-nine unrelated SJS/TEN patients and 128 unrelated healthy individuals were studied. Genomic extraction was carried out from complete blood samples using the salting out method. The PCR–RFLP method was used to amplify the following polymorphisms: TNF-α-308, IFN-γ +874, IL-10-1082, IL-13 Arg130Gln, and IL-4R Gln551Arg. TNF-α-308, IL-10-1082, IL-13 Arg130Gln, and IL-4R Gln551Arg polymorphisms were not associated with the genetic susceptibility to SJS/TEN. The distribution of TT, TA, AA genotypes of IFN-γ +874 was significantly different in SJS/TEN patients compared with controls (pC = 0.012). TA and AA genotypes were grouped to highlight the differences between patients and controls given by the absence of the AA genotype in the group of patients (pC = 0.03, OR = 3.61 95 % CI 1.20–11.6). This preliminary study suggests that IFN-γ +874 T/A polymorphism is associated with SJS/TEN.     

Pretibial myxedema is associated with polymorphism in exon 1 of CTLA-4 gene in patients with Graves’ ophthalmopathy

Cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) is a well-known molecule that regulates T cell activity, with polymorphisms at different regions of this gene having been associated with autoimmune conditions. Pretibial myxedema (PTM), also called Graves’ dermopathy, is an autoimmune extrathyroidal manifestation of Graves’ disease. We opted to investigate the relationship between three single nucleotide polymorphisms of the CTLA-4 gene (+49A/G, and −318C/T and −1147C/T) and PTM in Iranian patients with Graves’ ophthalmopathy (GO). A total of 105 unrelated Iranian patients with GO from the outpatient endocrine clinic of a large university general hospital as well as 103 healthy controls were studied. The genomic DNA was extracted from venous blood samples by a salting out method, and the polymorphisms at +49, −318 and −1147 positions of the CTLA-4 gene were determined using the polymerase chain reaction-restriction fragment length polymorphism method. The GG genotype (OR = 6.000, 95% CI = 1.805–19.940, P = 0.005) and the G allele (OR = 2.653, 95% CI = 1.314–5.357, P = 0.009) at position +49 were significantly associated with PTM in the patient group. The same genotype and allele were also significantly more common among patients (with or without PTM) than controls. No significant association was found for the other two polymorphisms. In conclusion, the +49G allele is associated with increased risk of PTM in patients with GO. Studies with larger sample sizes are needed to confirm the results of the present study.     

Study of genetic polymorphisms in the tumor necrosis factor α promoter region in Spanish patients with psoriasis

BackgroundSeveral studies have reported an association between tumor necrosis factor α (TNF-α) polymorphisms and inflammatory diseases such as psoriasis vulgaris and psoriatic arthritis, although the results vary according to the population studied. No studies have been performed in the Spanish population.ObjectiveTo analyze the polymorphisms of the promoter region of the TNF-α gene in patients with moderate to severe psorasis and to identify potential differences in genotype compared to a group of healthy volunteers.Material and methodsEighty-nine patients with moderate to severe psoriasis and 76 healthy controls with no personal or family history of psoriasis were selected. Polymorphisms of the TNF-α promoter region of both groups were genotyped.ResultsWe observed a higher prevalence of the genotype with both wild-type alleles at positions -238 (GG genotype, 86.5% vs 70.4%, respectively) and -1031 (TT genotype, 80.2% vs 45.8%, respectively) in patients compared to the healthy control group. The differences at positions -308 and -857 were not significant.ConclusionThere are differences in polymorphisms at positions -238 and -1031 in patients with moderate to severe psoriasis compared to healthy volunteers. This observation provides further support for the importance of the part that TNF-α plays in the pathophysiology of this disease.     

Association of HLA alleles and haplotypes with vitiligo in Moroccan patients: a case–control study

The aim of this study was to identify HLA class II alleles that may be involved in vitiligo genetic susceptibility in the Moroccan population and to determine susceptible and protective HLA alleles/haplotypes in vitiligo. One-hundred unrelated vitiligo patients and 300 healthy unrelated controls were studied for HLA class II alleles by polymerase chain reaction-sequence-specific primers. The phenotypic frequency of DRB1*07 (OR = 2.23, p _c = 0.014) was significantly higher, while that of DRB1*03 (OR = 0.40, p _c = 0.014) was significantly lower in patients than in controls. Haplotype DRB1*07–DQB1*02 (OR = 2.25, p _c = 0.024) was positively associated with vitiligo patients, while haplotype DRB1*03–DQB1*02 (OR = 0.35, p _c = 0.012) was negatively associated with this group. Vitiligo patients with positive family history and negative anti-thyroid peroxidase antibody (anti-TPO) have an extremely high phenotype frequency of DRB1*07–DQB1*02 haplotype (OR = 2.91, p _c = 0.048 and OR = 2.62, p _c = 0.00475, respectively). DRB1*03–DQB1*02 (OR = 0.32, p _c = 0.048 and OR = 0.38, p _c = 0.048, respectively) was negatively associated with patients without a family history and negative anti-TPO. This study demonstrated the positive association of HLA class II alleles and haplotypes with vitiligo in the Moroccan population. There may be differences in HLA haplotypes distribution in patients according to family history and anti-TPO profile.     

Serum levels of GRO-α are elevated in association with disease activity in patients with Behçet's disease

Background Although the etiology of Behçet’s disease (BD) is still unknown, neutrophils are implicated in its pathogenesis. Growth‐related oncogene‐α (GRO‐α) is a potent chemoattractant and activator for neutrophils. Objective To determine the role of GRO‐α in the pathogenesis of BD, we investigated serum GRO‐α levels in patients with BD. Materials and methods Sera from patients with BD (n = 57) and control subjects (n = 26) were measured by enzyme‐linked immunosorbent assay. Serum levels of GRO‐α were compared with clinical symptoms. Results Patients with BD had significantly elevated serum GRO‐α levels compared with healthy controls (121.7 ± 79.2 pg/ml vs. 75.9 ± 20.6 pg/ml, P < 0.01). Concerning the subgroups of BD, serum GRO‐α levels in active patients with BD (n = 35) were significantly higher than in inactive patients with BD (n = 22; 139.0 ± 92.8 pg/ml vs. 94.3 ± 36.2 pg/ml, P < 0.05). Also, as seen in previous studies, serum interleukin‐8 levels in patients with BD (52.4 ± 81.8 pg/ml) were significantly higher than in controls (13.9 ± 19.7 pg/ml, P < 0.01). Enhanced GRO‐α levels correlated with clinical symptoms such as erythema nodosum. Conclusion Our results indicate that serum levels of GRO‐α are elevated in patients with active stage BD, suggesting that GRO‐α may serve as a reliable marker for disease activity of BD.     

Evaluation of leptin level and Ob gene polymorphism in patients with Behcet’s disease

The present study was aimed to evaluate serum leptin level and the frequency of oligopolymorphic codon 25 (CAA/CAG) of Ob gene in Behcet’s disease. Eighty-seven patients with Behcet’s disease and 85 healthy controls with matched age, gender and body mass index were included in the study. Serum leptin level was determined and genotype of codon 25 of Ob gene was performed by using the PCR amplification after DNA extraction. Serum leptin concentration of the patients with Behcet’s disease (23.8 ± 22.8 ng/ml) was higher than that of the control groups (17.1 ± 14.7 ng/ml). The patients with Behcet’s disease and control subjects showed CAA/CAA genotype, indicating the presence of no polymorphism. Neither Behcet’s disease nor serum leptin level was found to be related to codon 25 polymorphism. We concluded that leptin 25CAG polymorphism is not associated with Behcet’s disease and serum leptin level.     

Lack of evidence for association between endothelial nitric oxide synthase gene polymorphism (glu298asp) with Behçet’s disease in the Turkish population

Endothelial nitric oxide synthase (eNOS) could be a candidate gene for Behçet’s disease (BD). This study investigated the relationship of the eNOS Glu²⁹⁸→Asp polymorphism with the presence and severity of BD in the Turkish population. Ninety-two patients with BD and 100 controls were studied. Analyses of Glu298Asp polymorphism in exon 7 of the eNOS gene were made by the polymerase chain reaction (PCR)-restriction fragment length polymorphism technique. The frequencies of the eNOS genotypes were similar for BD patients (GG:GT:TT=58.7%:38%:3.3%) and controls (59.2%:33.7%:7.1 %), P=0.335. No evidence of difference was found in the frequency of the T allele between BD patients (22.3%) and controls (24%), [OR=0.91, 95% CI (0.55–1.50), P=0.690]. Glu²⁹⁸→Asp polymorphism of the eNOS gene does not appear to be associated with the presence of BD in the Turkish population.     

Pathogenetic mechanisms of vitiligo in a patient with Sézary syndrome

Patients exhibiting association between vitiligo and cutaneous T-cell lymphoma (CTCL) remain rare and it is not known whether some T-cell subpopulations of CTCL in the skin are able to recognize specific melanocytic epitopes and thus induce vitiligo. The aim of our study was to determine whether T cells specific to melanocyte differentiation antigens were detectable among tumour-infiltrating lymphocytes (TIL) in the hypopigmented skin of a patient with Sézary syndrome (SS). A 71-year-old patient presented with SS and developed vitiligo during the course of her disease. Immunohistochemical studies showed staining with HMB45 and MelanA antibodies in the pigmented skin biopsy, whereas no staining was observed in the hypopigmented skin biopsy. To analyse responses to melanocyte differentiation antigens, we used a transient COS transfection assay that permits an estimation of CD8 T-cell responses against a large number of HLA/antigen combinations. This technique allowed the detection of melanocyte differentiation antigen-specific T lymphocytes, directed mainly against Melan-A/MART1 antigen in the HLA-A*23 context. Our study supports the concept that vitiligo that has developed during the evolution of a CTCL is related to the presence of a T-lymphocyte subpopulation reactive against melanocyte differentiation antigens (mainly Melan-A/MART1) present in skin lesions. The role of interferon in the induction of this T-lymphocyte subpopulation is discussed.     

Compound glycyrrhizin tablets combined with the 308 nm excimer laser in the treatment of vitiligo: A systematic review and meta-analysis

Background

Although the 308 nm excimer laser is commonly used to cure vitiligo, its clinical efficacy is limited. Experts have found that the efficacy of compound glycyrrhizin tablets combined with the 308 nm excimer laser in the treatment of vitiligo is significantly enhanced, but the specific research methods and clinical data must be clarified.

Objective

To determine the clinical efficacy of compound glycyrrhizin tablets combined with the 308 nm excimer laser in the treatment of vitiligo.

Methods

Until August 2022, studies were searched in PubMed, the Cochrane Library, the Chinese Biomedical Literature Database, the China National Knowledge Infrastructure, the Chinese Scientific Journal Database, and the Wan Fang Database. We also searched for clinical RCTs involving compound glycyrrhizin tablets combined with the 308 nm excimer laser for the treatment of vitiligo. The meta-analysis was conducted in accordance with the Cochrane Handbook's recommendations. Two reviewers regulated the study selection, data extraction, and assessment of bias risk, and consulted a third reviewer as necessary. For the meta-analysis, Review Manager 5.4 was utilized.

Results

Finally, 9 articles and 1052 patients were included. A systematic review compared the efficacy of compound glycyrrhizin tablets combined with the 308 nm excimer laser to that of the 308 nm excimer laser alone: OR = 3.33, p < 0.00001, 95% confidence interval [2.25, 4.92].

Conclusion

In the treatment of vitiligo, compound glycyrrhizin tablets combined with the 308 nm excimer laser are more effective than the 308 nm excimer laser alone, and there are no serious adverse reactions. It is a safe and efficient way of treatment.     

Apolipoprotein E polymorphism and lipoprotein compositions in patients with Behçet's disease

Background Behçet's disease (BD) is a multisystemic disease of unknown etiology characterized by chronic relapsing oral–genital ulcers and uveitis. Some abnormalities in lipoprotein metabolism have been described in patients with BD. Methods In this study, apolipoprotein E (apo E) polymorphism and lipoprotein cholesterol concentrations in 30 patients with BD were compared with those of 27 control subjects. Results Both patients and controls were found to be normolipidemic. Patients with BD had significantly higher concentrations of high‐density lipoprotein (HDL) cholesterol than those of controls (P < 0.05); however, there was no difference in serum triglyceride, low‐density lipoprotein (LDL) and very low‐density lipoprotein (VLDL) cholesterol concentrations. The distribution of apo E genotypes and alleles was the same in both groups. There were slight differences in allele frequency between the groups, but this was not statistically significant. Conclusions The high HDL cholesterol levels observed in our patients were not related to abnormalities in apo E alleles.     

A comparative study of oxidant–antioxidant status in stable and active vitiligo patients

The pathogenetic mechanisms in vitiligo have not been completely clarified. One of the major hypotheses in the pathogenesis of vitiligo is the oxidative stress hypothesis. The active or stable phase of vitiligo is defined on the basis of the progression or appearance of new lesions in the last 3 months and the absence of new lesions or their progression in the last 6 months, respectively. Eighteen patients with active vitiligo, 18 patients with stable vitiligo, and 40 controls were included in this study. We examined serum levels of malondialdehyde, selenium, vitamin E and A, and the erythrocyte activities of glutathione peroxidase, superoxide dismutase, and catalase. Our results revealed a significantly higher level of serum malondialdehyde, selenium in patients with active disease compared with the controls. Significant higher increase in erythrocytes superoxide dismutase activities was observed in active vitiligo group, erythrocyte glutathione peroxidase activity was decreased significantly in active disease, whereas erythrocyte catalase activity and plasma vitamin E and A levels were not different in vitiligo patients as compared with controls. Our study shows that oxidative stress is involved in the pathophysiology of both active and stable vitiligo but increased imbalance of antioxidants was observed in the blood of active vitiligo patients.I dedicate this article to our dear director (Mme Hentati Basma) who dead in 06/06/06. We will never forget you and you are always in our heart.