Inducible Nitric Oxide Synthase iNOS-954-G>C and Ex16+14-C>T Gene Polymorphisms and Susceptibility to Vitiligo in the Saudi Population.

Objective: Vitiligo is an acquired pigmentary skin disorder with regional disappearance of melanocytes. Multigenic inheritance has been proposed in the pathogenesis of vitiligo. The present study aimed to investigate the possible association of inducible nitric oxide synthase polymorphisms iNOS-954-G/C (rs1800482 G>C) and iNOS-Ex16+14-C/T (rs2297518 C>T) with vitiligo in the Saudi population, if any. Methods: We included 120 vitiligo cases and an equal number of age matched healthy controls. Polymerase chain reaction with restriction fragment length polymorphism method was used for the analysis of genetic polymorphisms. Results: The heterozygous (GC), (GC + CC) combined genotype and variant allele; C allele of rs1800482 G>C were associated significantly (p < 0.005, after Bonferroni correction) with increased risk of vitiligo (OR = 3.46, 95% CI = 1.99-6.01, p = 0.001), (OR = 3.30, 95% CI= 1.93-5.65, p = 0.001) and (OR = 1.94, 95% CI = 1.31-2.87, p = 0.001) respectively. When GC genotype of rs1800482 G>C was co-inherited with common genotype (CC) and heterozygous genotype (CT) of rs2297518 C>T, the risk of vitiligo was significantly increased ((OR = 4.51, 95% CI = 2.18-9.33, p = 0.001) and (OR = 3.60, 95% CI = 1.61-8.01, p = 0.001)) respectively. None of the rs1800482 G>C and rs2297518 C>T genotypes and alleles have been associated with non-segmental vitiligo in terms of gender, age of onset, and types of vitiligo. Conclusion: The heterozygous (GC), (GC+CC) combined genotype and variants allele; C allele of rs1800482 G>C, may cause overproduction of NO, which has been linked to melanocyte loss by increasing oxidative stress and decreasing melanocyte adhesion to the extracellular matrix components, and thus could be an associative risk factor for vitiligo.

Dinuclear uranium(VI) salen coordination compound: an efficient visible-light-active catalyst for selective reduction of CO2 to methanol.

A new dinuclear uranyl salen coordination compound, [(UO2)2(L)2]·2MeCN [L = 6,6'-((1E,1'E)-((2,2-dimethylpropane-1,3-diyl)bis(azaneylylidene))-bis(methaneylylidene))bis(2-methoxyphenol)], was synthesized using a multifunctional salen ligand to harvest visible light for the selective photocatalytic reduction of CO2 to MeOH. The assembling of the two U centers into one coordination moiety via a chelating-bridging doubly deprotonated tetradentate ligand allowed the formation of U centers with distorted pentagonal bipyramid geometry. Such construction of compounds leads to excellent activity for the photocatalytic reduction of CO2, permitting a production rate of 1.29 mmol g-1 h-1 of MeOH with an apparent quantum yield of 18%. Triethanolamine (TEOA) was used as a sacrificial electron donor to carry out the photocatalytic reduction of CO2. The selective methanol formation was purely a photocatalytic phenomenon and confirmed using isotopically labeled 13CO2 and product analysis by 13C-NMR spectroscopy. The spectroscopic studies also confirmed the interaction of CO2 with the molecule of the title complex. The results of these efforts made it possible to understand the reaction mechanism using ESI-mass spectrometry.

Association of Functional Polymorphism in Protein Tyrosine Phosphatase Nonreceptor 22 (PTPN22) Gene with Vitiligo.

The protein tyrosine phosphatase nonreceptor 22 (PTPN22) is associated with susceptibility to autoimmune diseases. The functional polymorphism in PTPN22 at 1857 is a strong risk factor for vitiligo susceptibility in Europeans; however, controversy exits in other populations. Present study was aimed to determine whether the PTPN22 C1857T polymorphism confers susceptibility to vitiligo in Saudi Arabians. Genomic DNA was extracted and amplified using tetra primer amplification-refractory mutation system polymerase chain reaction (ARMS-PCR) method. The frequencies of allele T and genotype CT of PTPN22 C1858T polymorphism were significantly higher, whereas those of allele C and genotype CC were lower in patients as compared with controls (P < 0.0001). The genotype TT was absent in both the patients and controls. It is concluded that PTPN22 C1858T polymorphism is strongly associated with vitiligo susceptibility. However, additional studies are warranted using large number of samples from different ethnicities and geographical areas.

Cytokine Gene Polymorphisms in Saudi Patients With Atopic Dermatitis: A Case-Control Study.

The cause of atopic dermatitis (AD) is multifactorial and a number of genes including cytokines have been involved. We genotyped 315 subjects for polymorphisms in TNF-α and TNF-ß and IL-10 genes. Patients had significantly higher frequency of GA genotype of TNF-α (-308 G/A) than healthy controls. Patients with AD and controls had similar distribution of A and G alleles. Genotype AA was found in 7.11% of controls while completely absent in cases. The frequencies of genotypes GG and AA of TNF-ß (+252 A/G) polymorphism were higher whereas the frequency of genotype GA was significantly lower in patients than the controls. The frequencies of genotypes GG and AA of IL-10 (1082 G/A) polymorphism were significantly increased whereas genotype GA was decreased in patients than the controls. It is concluded that TNF-α (-308 G/A), TNF-ß (+252 A/G), and IL-10 (-1082 G/A) polymorphisms are linked with the susceptibility of AD in Saudis and can be a risk factor.

The Protein Tyrosine Phosphatase Nonreceptor 22 (PTPN22) R620W Functional Polymorphism in Psoriasis.

BACKGROUND: Psoriasis is a complex autoimmune disease caused by the interaction of genetic and environmental factors. PTPN22 gene polymorphism has been reported to affect psoriasis susceptibility; however, no data are available for Middle Eastern populations. OBJECTIVE: The aim of this study was to investigate the association of PTPN22 (1858C/T) R620W polymorphism with psoriasis in a Saudi cohort. METHODS: Saudi subjects (n = 306) including patients with psoriasis (n = 106) and matched controls (n = 200) were studied for PTPN22 variants using tetra-primer amplification refractory mutation system-polymerase chain reaction method. The frequencies of alleles and genotypes of PTPN22 (1858C/T) polymorphism were compared between patients and controls. RESULTS: The frequency of CT genotype of PTPN22 (1858C/T) polymorphism was significantly higher, whereas that of CC genotype was lower in patients with psoriasis than in controls (P < .001, relative risk [RR] = 7.151). The homozygous genotype TT was absent in both the patients and healthy controls. The frequency of allele T encoding tryptophan (W) was significantly increased (P < .001, RR = 5.76), whereas that of allele C encoding arginine (R) decreased in psoriasis cases as compared with controls (P < .001, RR = 0.173) indicating that individuals carrying allele T are more susceptible to psoriasis than noncarriers. CONCLUSIONS: PTPN22 (1858C/T) polymorphism is positively associated with susceptibility of psoriasis in Saudis and can be developed as biomarker for evaluating psoriasis risk. However, further studies on PTPN22 polymorphism in larger samples from different geographical areas and ethnicity are warranted.

Scorpion (Androctonus bicolor) venom exhibits cytotoxicity and induces cell cycle arrest and apoptosis in breast and colorectal cancer cell lines.

OBJECTIVES: The defective apoptosis is believed to play a major role in the survival and proliferation of neoplastic cells. Hence, the induction of apoptosis in cancer cells is one of the targets for cancer treatment. Researchers are considering scorpion venom as a potent natural source for cancer treatment because it contains many bioactive compounds. The main objective of the current study is to evaluate the anticancer property of Androctonus bicolor scorpion venom on cancer cells. MATERIALS AND METHODS: Scorpions were milked by electrical stimulation of telsons and lyophilized. The breast (MDA-MB-231) and colorectal (HCT-8) cancer cells were maintained in appropriate condition. The venom cytotoxicity was assessed by 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay, and the cellular and nuclear changes were studied with propidium iodide and 4',6-diamidino-2-phenylindole stain, respectively. The cell cycle arrest was examined using muse cell analyzer. RESULTS: The A. bicolor venom exerted cytotoxic effects on MDA-MB-231 and HCT-8 cells in a dose- and duration-dependent manner and induced apoptotic cell death. The treatment with this venom arrests the cancer cells in G0/G1 phase of cell cycle. CONCLUSIONS: The venom selectively induces the rate of apoptosis in MDA-MB-231 and HCT-8 cells as reflected by morphological and cell cycle studies. To the best of our knowledge, this is the first scientific evidence demonstrating the induction of apoptosis and cell cycle arrest by A. bicolor scorpion venom.

Association of genetic polymorphisms in interferon-γ, interleukin-6 and transforming growth factor-ß1 gene with oral lichen planus susceptibility.

BACKGROUND: Oral lichen planus (OLP) is a premalignant mucocutaneous disease in which genetic factors and immune responses play a major role. Cytokines play an important role in the pathogenesis and disease progression of OLP. The aim of this study was to investigate the impact of gene polymorphisms of T helper cell subtype Th1 and Th2 cytokines, interferon-gamma (IFN-γ), interleukin-6 (IL-6) and transforming growth factor (TGF)-ß1 on OLP susceptibility in a Saudi cohort. METHODS: Forty two unrelated patients with OLP and 195 healthy controls were genotyped for IFN-γ (874A/T), IL-6 (174G/C) and TGF-ß1 (509C/T) polymorphisms. RESULTS: The frequency of genotype AT of IFN-γ (874A/T) was significantly higher while genotype AA was lower in OLP patients as compared to controls (P < 0.05). The frequency of T containing genotypes (AT + TT) was also higher in OLP patients as compared to that in controls (P = 0.003). The frequencies of allele T was higher while that of allele A lower in patients than the controls however the difference was not statistically significant (P = 0.07). There was no significant difference in the frequencies of alleles and genotypes of IL-6 (174G/C) and TGF-ß1 (509C/T) polymorphisms between patient and control groups. These results indicated that genotype AT of IFN-γ (874A/T) polymorphism is associated with OLP risk and genotype AA is protective to OLP. On the other hand the polymorphisms IL-6 (174G/C) and TGF-ß1 (509C/T) may not be associated with OLP risk in our population. CONCLUSION: It is concluded that IFN-γ (874A/T) polymorphism is associated with the susceptibility of OLP, however further studies with large sample size involving different ethnic populations should be conducted to strengthen our results.

TNF-α, TNF-ß and IL-10 gene polymorphism and association with oral lichen planus risk in Saudi patients.

OBJECTIVES: Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease. Cytokines play an important role in the pathogenesis and disease progression of OLP. Various reports have implicated cytokine gene polymorphisms in susceptibility to develop some immune mediated conditions including OLP. The purpose of this study was to investigate the association of tumor necrosis factor (TNF)-α, TNF-ß and interleukin (IL)-10 gene polymorphisms with the OLP risk. MATERIAL AND METHODS: Forty two unrelated patients with OLP and 211 healthy volunteers were genotyped for TNF-α (-308 G/A), TNF-ß (+252A/G), IL-10 (-1082G/A), IL-10 (-819C/T), and IL-10 (-592C/A) polymorphisms. RESULTS: The frequencies of allele A and genotype GA of TNF-α (-308G/A) were significantly higher while allele G and GG genotypes were lower in OLP patients as compared to the controls (P<0.001). The frequency of GA genotype of TNF-ß (+252A/G) was significantly higher in patients than in controls while the AA genotype was completely absent in OLP patients. These results indicated that allele A and genotype GA of TNF-α (-308G/A) as well as the GA genotype of TNF-ß (+252A/G) polymorphisms are associated with OLP risk. The frequencies of alleles and genotypes of -1082G/A, -819C/T and -592C/A polymorphisms in IL-10 gene did not differ significantly between OLP patients and controls (P>0.05). However, haplotype ATA extracted from 1082G/A, -819C/T, -592C/A polymorphisms of IL-10 were more prevalent in OLP patients when compared to controls indicating its possible association with OLP susceptibility. CONCLUSION: It is concluded that TNF-α (-308G/A), TNF-ß (+252A/G) and IL-10 (-1082G/A, -819C/T and -592C/A) polymorphisms are associated with the susceptibility of OLP, thus giving additional support for the genetic basis of this disease.

TNF-α, TNF-ß and IL-10 gene polymorphism and association with oral lichen planus risk in Saudi patients

Objectives Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease. Cytokines play an important role in the pathogenesis and disease progression of OLP. Various reports have implicated cytokine gene polymorphisms in susceptibility to develop some immune mediated conditions including OLP. The purpose of this study was to investigate the association of tumor necrosis factor (TNF)-α, TNF-β and interleukin (IL)-10 gene polymorphisms with the OLP risk. Material and Methods Forty two unrelated patients with OLP and 211 healthy volunteers were genotyped for TNF-α (-308 G/A), TNF-β (+252A/G), IL-10 (-1082G/A), IL-10 (-819C/T), and IL-10 (-592C/A) polymorphisms. Results The frequencies of allele A and genotype GA of TNF-α (-308G/A) were significantly higher while allele G and GG genotypes were lower in OLP patients as compared to the controls (P<0.001). The frequency of GA genotype of TNF-β (+252A/G) was significantly higher in patients than in controls while the AA genotype was completely absent in OLP patients. These results indicated that allele A and genotype GA of TNF-α (-308G/A) as well as the GA genotype of TNF-β (+252A/G) polymorphisms are associated with OLP risk. The frequencies of alleles and genotypes of -1082G/A, -819C/T and -592C/A polymorphisms in IL-10 gene did not differ significantly between OLP patients and controls (P>0.05). However, haplotype ATA extracted from 1082G/A, -819C/T, -592C/A polymorphisms of IL-10 were more prevalent in OLP patients when compared to controls indicating its possible association with OLP susceptibility. Conclusion It is concluded that TNF-α (-308G/A), TNF-β (+252A/G) and IL-10 (-1082G/A, -819C/T and -592C/A) polymorphisms are associated with the susceptibility of OLP, thus giving additional support for the genetic basis of this disease. .

Apolipoprotein E gene polymorphism and serum lipid profile in Saudi patients with psoriasis.

BACKGROUND/AIM: Apolipoprotein E (APOE) gene variants have been reported to influence psoriasis risk. However, data is limited to a few ethnicities and no similar study has been performed in middle eastern populations. We investigated this association in Saudi psoriasis patients. METHODS: Saudi subjects (294) were genotyped for APOE gene using APOE StripAssay kit. RESULTS: The frequencies of alleles ε2, ε4, and genotypes ε3/ε4 and ε3/ε2 were significantly higher in psoriasis patients compared with those in controls. The frequency of ε3 allele and ε3/ε3 genotype was significantly lower in patients. Other genotypes, ε2/ε4, ε2/ε2, and ε4/ε4, were absent in both groups. The serum cholesterol, triglycerides, and LDL levels were significantly higher in psoriasis patients contrary to HDL level. Patients with APOE ε 4 had significantly higher levels of total cholesterol and LDL cholesterol, whereas those with the ε2 had higher HDL cholesterol, and triglycerides. CONCLUSION: APOE alleles ε2, ε4, and genotypes ε2/ε3 and ε4/ε3 are associated with psoriasis and can be a risk factor while allele ε3 and genotype ε3/ε3 may be protective for psoriasis in Saudis. Results of lipid profile support that psoriasis is one of the independent risk factors for hyperlipidemia and emphasize the need of screening cardiovascular diseases in psoriatic patients.

Characteristics of superficial fungal infections in the Riyadh region of Saudi Arabia.

BACKGROUND: The prevalence and characteristics of superficial fungal infections (SFIs) vary with climatic conditions, lifestyle, and population migration patterns. This study was undertaken to determine the characteristics of SFIs amongst patients visiting the dermatology clinic of Riyadh Military Hospital, Riyadh, Saudi Arabia, during the period 2003-2005. METHODS: One hundred and nineteen patients with confirmed SFI (37 males and 82 females), aged between 5 months and 67 years, were included in this study. The diagnosis of SFI was based on clinical presentation confirmed by laboratory analysis. The type of mycotic pathogen and the site of infection were recorded as a function of age and sex. RESULTS: Onychomycosis (40.3%) was the most frequent infection, followed by tinea capitis (21.9%), tinea pedis (16%), tinea cruris (15.1%), and tinea corporis (6.7%). Tinea capitis was most prevalent (15.1%) in children (male to female ratio, 1 : 1.57), whereas tinea pedis was most common (11.8%) in adults (male to female ratio, 1 : 2.5). Trichophyton mentagrophytes and Microsporum canis were the most common dermatophytes responsible for tinea infections, and T. mentagrophytes, Candida spp., and Aspergillus spp. were mainly responsible for onychomycosis. CONCLUSION: The prevalence of SFI was twofold greater in females than males. Children were most commonly affected by tinea capitis, whereas adults generally suffered from tinea pedis. The frequency of onychomycosis was nearly three times higher in adults. This study clearly shows that SFIs are of concern in both genders and in all age groups.

Association of Interleukin-10 gene promoter polymorphisms in Saudi patients with vitiligo.

The promoter region of human Interleukin -10 gene is highly polymorphic and has been associated with numerous autoimmune diseases. Recent studies have linked vitiligo with defective autoimmune system. This study is aimed to explore a possible association between IL-10 gene polymorphism and vitiligo in Saudi population. This case control study consisted of 184 Saudi subjects including 83 vitiligo patients (40 males, 43 females mean age 27.85 +/- 12.43 years) and 101 matched controls. Genomic DNA was extracted from the blood samples of healthy controls and Vitiligo patients visiting out patient clinic of Department of Dermatology, Riyadh Armed Forces Hospital, using QIA ampR DNA mini kit (Qiagen CA, USA). Interleukin-10 gene was amplified by polymerase chain reaction (PCR) using Arms primers to detect any polymorphism involved at positions -592, -819 and -1082. The frequencies of GG genotype at -1082, and CC genotype at positions -592 and 819 were significantly higher in vitiligo patients compared to healthy subjects suggesting that GG and CC genotypes might be susceptible to vitiligo in Saudis. On the other hand genotypes -1082 GA, -819 CT, and -592 CA of IL-10 were more prevalent in healthy controls suggesting protective effects of GA, CT and CA genotypes against vitiligo. This study indicates that the IL-10 gene may play a significant role in the etiology of vitiligo among Saudis.

Association of HLA loci alleles and antigens in Saudi patients with vitiligo.

HLA complex is composed of several closely linked loci, each containing several alleles, yielding a high expression of polymorphism. Vitiligo, a commonly acquired dermatological disorder, has been associated with different HLA antigens in different ethnic groups. In this study, HLA classes I (HLA-A, B, and C) and II (HLA-DR, DQ) antigens/alleles were analyzed in a group of 80 Saudi subjects consisting of vitiligo patients (40) and matched controls (40). The frequency of antigens of various HLA loci was tested using two-stage microcytotoxicity assays, while the frequency of alleles of HLA-DR was screened by polymerase chain reaction/sequence specific primers (PCR/SSP) method. The frequencies of HLA-B7, B15, Bw6, Cw6, Cw7, and DRB4*010101 were found to be significantly higher in vitiligo patients compared to controls [P = 0.029, 0.015, 0.033, 0.009, 0.043, and 0.015, respectively, with relative risk (RR) > or = 3, etiologic fraction (EF) > or = 0.4]. On the other hand, HLA-A9, B5, DQ1, and DRB3*010101 were significantly decreased in vitiligo patients compared to healthy Saudis [P = 0.008, 0.004, 0.028, and 0.04, respectively, with RR < 1 and preventive fraction (PF) < 0.5]. Among the patients, the highest allele frequency was noted for DRB4*010101(70%), while in controls it was for DRB3*010101 (72.5%). These results for antigens and allele frequency of various HLA Loci in vitiligo patients and control subjects suggested that HLA-B7, Bw6, Cw6, Cw7, and DRB4*010101 could be susceptible to vitiligo, while HLA-A9, B5, DQ1, and DRB3*010101 might be negatively associated with the development of vitiligo in Saudis.

Study of alanine-73 and aspartate-9 of HLA-C locus in Saudi psoriasis patients, using sequence-specific primers (PCR-SSP).

Alanine at residue 73 (Ala-73) and aspartate at residue 9 (Asp-9) are characteristic to both Cw6 and Cw7 alleles of HLA-C gene and have been suggested as possible markers for psoriasis vulgaris (PsV). However, the results from various ethnic groups/populations are contradictory and inconclusive. In this study, an attempt has been made to examine the association between HLA-C (Ala-73 and Asp-9) and susceptibility to PsV among Saudi patients. Genomic DNA was extracted from 25 Saudi PsV patients and 75 control subjects. Polymerase chain reaction (PCR) was performed to amplify HLA-C sequences using earlier reported primers, C133P and C243PR. Sequence-specific primers were used to specifically detect nucleotide coding for Ala-73 and Asp-9 in all the subjects. The results showed significantly higher frequency of Asp-9 (84.0 % versus 61.3 %) in PsV patients as compared to controls (p < 0.05, 2-tailed Fisher's exact test). The frequencies of Ala-73 among PsV patients (92 %) and controls (88 %) did not differ significantly.