Higher Expression of Toll-like Receptors 3, 7, 8, and 9 in Pityriasis Rosea

BACKGROUND: Pityriasis rosea (PR) is a common papulosquamous skin disease in which an infective agent may be implicated. Toll-like receptors (TLRs) play an important role in immune responses and in the pathophysiology of inflammatory skin diseases. Our aim was to determine the possible roles of TLRs 3, 7, 8, and 9 in the pathogenesis of PR. METHODS: Twenty-four PR patients and 24 healthy individuals (as controls) were included in this case control study. All recruits were subjected to routine laboratory investigations. Biopsies were obtained from one active PR lesion and from healthy skin of controls for the detection of TLR 3, 7, 8, and 9 gene expression using real-time polymerase chain reaction. RESULTS: This study included 24 patients (8 females and 16 males) with active PR lesions, with a mean age of 28.62 years. Twenty four healthy age- and sex-matched individuals were included as controls (8 females and 16 males, with a mean age of 30.83 years). The results of the routine laboratory tests revealed no significant differences between both groups. Significantly elevated expression of all studied TLRs were detected in PR patients relative to healthy controls (p < .001). CONCLUSIONS: TLRs 3, 7, 8, and 9 might be involved in the pathogenesis of PR.

Low incidence of androgen receptor mutation among Egyptian children with androgen resistance

In Egypt, disorders of sex development [DSD] constitute a significant entity among the birth defect list. Previous studies have reported that end organ androgen unresponsiveness, i.e. Androgen resistance, was the most prevalent underlying mechanism among Egyptian 46, XY DSD cases. Based on cytogenetic and hormonal diagnostic criteria as well as few sporadic case reports, it was proposed that androgen receptor [AR] defects [i.e. Androgen insensitivity syndrome [AIS], OMIM#300068] might constitute a major etiology within this category. However, this has never been systematically ascertained through an AR molecular diagnostic approach. The current study aimed to assess the role of AR mutations as an underlying etiology among a sample of Egyptian 46,XY DSD pediatric patients presenting with androgen end organ unresponsiveness. In the current study, 21 children [age <18years] with male undermasculinization due to androgen end organ unresponsiveness were selected from 46, XY DSD cases. The selection criteria included ambiguous genital phenotype or genitalia discordant to the genotypic sex; 46,XY Karyotype and normal testicular response to HCG stimulation in prepubertal -patients or normal basal testosterone [T] levels in postpubertal subjects. Molecular studies of the AR entailed PCR amplification for screening of major deletions/ insertions, single stranded conformational polymorphism [SSCP] screening for point mutations in the AR 2-8 exons followed by sequencing of these exons for all cases. The results showed that none had major deletions/insertions. Five exons out of 147 [3.4%] showed abnormal SSCP migrational patterns. Out of those 5, two mutations in two Egyptian patients were detected by sequencing. The first was R840G [Arginine 840 glycine], in exon 7 [The ligand binding domain]. The other was A596T [Alanine 596 Threonine] in exon 3 [The DNA binding domain]. This study shows that AR mutation is an uncommon underlying etiology among Egyptian paediatric 46,XY cases

Implication of glutathione S-transferase M1 and T1 polymorphisms in the development of senile cataract among Egyptians

Cataract, or opacification of the lens, is one of the most common causes of loss of useful vision among Egyptians. Currently, surgery is the only approach for the treatment of cataract and the etiology of age-related changes in the lens is not fully understood. Oxidative damage and genetic factors have a major role in the development of age related cataract. Glutathione is the most abundant non-protein intracellular thiol, with multiple roles as antioxidant agent, and the glutathione S-transferases [GSTs] are group of polymorphic enzymes that are important in protection against oxidative damage, as they dethiolate protein-S-S-glutathione in the human lens. The study aimed to determine the effect of genetic polyorphisms of Glutathione S-transferases M1 and T1 on the risk of senile cataract in Egyptian population. Using a multiplex polymerase chain reaction [PCR], the GSTM1 and GSTT1 gene polymorphisms were evaluated in 53 Egyptian patients with senile cataract and in 73 otherwise healthy control group with matched age and sex distribution. Serum GST activity, the level of Malondiableyde [a lipid peroxidation product] and the blood level of reduced glutathione [GSH] were estimated. The frequency of the GSTM1 positive individuals among the senile cataract group was significantly higher than in controls [57 vs 37%] with odds ratio 2.22 95% CI:1.08-4.573; p=0.029]. The risk among the GSTM1 positive individuals of developing senile caaract was even higher in female subjects: 68% of females were GSTM1 positive in the cataract group while only 38% of females had GSTM1 positive genotype in controls [OR=3.4; 95% CI: 1.284-9.067; p=0.012]. combination of "GSTM1 positive and GSTT1 positive" genotypes [OR = 2.16; 95% CI: 0998-4.68; P=0.049]. However the combination of "GSTM1 null, GSTT1 positive" was found to be protective from the development of senile cataract [OR=0.47; 95% CI: 0.22-0.99; p=0.045]. The study also showed significantly deceased serum level of GST and reduced glutathione [GSH] and increased level of malondialdehyde [MDA] in senile cataract patients relative to controls [p>0.001]. The present study suggests that the GSTM1 positive genotype and the combined "GSTM1 positive/GSTT1 positive" genotype may be associated with increased risk of development of senile cataract. However the "GSTM1 null/GSTT1 positive" genotype was found to be protective from the development of cataract in the Egyptian population. The correlation between polymorphic GSTs with the other cataractogenic genetic and environmental factors is highly complicated so, the study also, suggests that when evaluating the role of a particular GST gene in any disease susceptibility, the whole pattern of different biotransformation enzymes should be taken into account as much as possible. The importance to further evaluate this matter is related to the possibility of developing diagnostic tool for predicting, by non-invasive genotype analysis, the inter-individual susceptibility to the disease

Phenylalanine hydroxylase VNTR polymorphism patterns among Egyptian normal and phenylketonuric subjects

Analysis of the polymorphic variable number of tandem repeats [VNTR] is a powerful tool for detection of DNA variation among normal individuals within a population, as well as testing linkage to disease-underlying mutations in various ethnic groups. Phenylketonuria [PKU] is caused by mutations in the phenylalanine hydroxylase [PAH] gene, which has a VNTR region at the 3 end. In this work, we report on the PAH VNTR polymorphism patterns among a sample of the Egyptian population and a large number of PKU cases. The study included 77 normal subjects and 87 phenylketonuric probands. Genomic DNA was extracted from leukocytes using the salting out technique. DNA amplification using specific primers and the polymerase chain reaction was used to detect the various VNTR patterns. The VNTR heterozygosity index was 56% and 21% in the normal and PKU groups, respectively. The VNTR homozygosity index was comparably high in patients with IVS10-11 G>A and R261Q mutations, [i.e. > 80%]. An unusually high prevalence of the 8-RU and 10-RU alleles among non-IVS1011 G>A/non-R261Q PKU cases was noted. The VNTR patterns in both normal and PKU-affected Egyptians were highly heterogeneous. Moreover, both IVS10-11 G>A and R261Q showed previously unreported VNTR patterns. In conclusion, the study of PAH VNTR allele patterns among normal and PKU-affected Egyptian subjects has confirmed the high heterogeneity of the normal Egyptian population as well as the PKU patients