disintegrin and metalloproteinase 33 [ADAM33] gene polymorphism association with asthma in Egyptian children

A disintegrin and metalloproteinase-encoding gene [ADAM33], was recently identified as an asthma susceptibility gene. ADAM33 protein is expressed in smooth muscle cells of bronchi and pulmonary fibroblasts, playing a major role in airway remodeling. Earlier studies, have mostly confirmed a link between ADAM33 and asthma as well as bronchial hyperresponsiveness. This work studied a group of Egyptian asthmatic children for 3 ADAM33 single nucleotide polymorphisms [SNPs], previously identified as putative risk alleles: T1 G > A[rs2280091], T2 A > G[rs2280090], V4 G > C[rs2787094] using Polymerase Chain Reaction - restriction fragment length polymorphism [PCRRFLP] with emphasis on their relation to clinical [severity, smoking, family history, and atopic manifestations] and laboratory data [Ig Immunoglobulin E [Ig E] level and absolute eosinophilia] and pulmonary functions. Sixty [3-12 years old] asthmatic children and 32 matched controls were recruited. The genotype distribution for the SNPs showed no significant difference between the patients and the controls. A higher frequency of the [AA] genotype of T1 polymorphism was found in controls [75%] than in patients [41%], while the [AG] variant was higher in cases [46.6%] than in controls [21.9%] but with no statistically significant difference. Also the [GG] genotype was higher in cases [11.6%] than in controls [3.1%] but with no statistical significance. The allelic frequencies of T1 showed a higher [A] allele in controls [85.93%] than cases [65%] and higher [G] allele in cases [35%] than controls [14.06%], showing a high significant difference. No correlation was found between [T1, T2, and V4] and the demographic, clinical and laboratory parameters, except SNP T1 showing a positive correlation with Ig E level, and SNP V4 showing a positive correlation with passive smoking as a precipitating factor and borderline significance with absolute eosinophilia. In conclusion, no significant association was detected between these SNPs and asthma susceptibility in this study

Genetic polymorphisms of DNA repair gene XRCC1 and susceptibility to acute leukemia

Defective DNA repair has been reported to be a risk factor for various malignancies. Polymorphisms of DNA repair genes could alter protein structure and may impair DNA repair capacity. Genetic polymorphisms of XRCC1 gene could lead to defective base excision repair [BER] pathway resulting in impaired DNA repair capacity and increased risk of acute leukemia. To determine the possible effect of XRCC1 gene polymorphisms 194Arg to Trp and 399Arg to Gin on the risk of development of acute leukemia in a group of Egyptian patients. The study was also extended to evaluate the association between these polymorphisms and disease outcome. Polymorphisms of XRCC1 codon 194 [Arg to Trp] and codon 399 [Arg to Gin] were genotyped in 35 patients with acute lymphoblastic leukemia [ALL], 35 patients with acute myeloid leukemia [AML] and 70 healthy controls using polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] method. Individuals with heterozygous XRCC1 194 Arg/Trp variant demonstrated a significant increased risk of AML than controls [Odds Ratio [OR] 3.5, 95% confidence interval [CI], 1.3-9.5]. The frequency of homozygous XRCC1 399 Gin/Gin variant was statistically higher in ALL patients than controls [OR 3.69, 95% CI, 1.19-11.4]. Stratification for sex with regard to codon 194Trp carriers showed that males had 3.2-fold increased risk of ALL than females with borderline significance. In case of codon 399Gln polymorphism, a highly significant risk of ALL among females was observed with 7.5-fold increased risk. The frequency of XRCC1 haplotype A [399Gln carriers and 194Trp carriers] was significantly higher in both ALL and AML patients than controls [OR5.2, 95% CI, 1.6-16.7, p-value <0.01 for ALL] [OR 3.2, 95% CI, 0.9-11.1, p-value=0.055 for AML]. The polymorphic variant of XRCC1 194Trp has a significant unfavorable effect on disease outcome among ALL and AML patients [p-value 0.002 and 0.05 respectively]. Acute lymophoblastic leukemia patients carrying the 399Gln allele experienced a significant unfavorable outcome than ALL patients carrying the wild-type allele [p-value<0.01]. An increased risk of AML among carriers of XRCC1 194Trp and an increased risk of ALL among patients with XRCC1 399Gln variant genotypes were observed. Combined presence of XRCC1 194Trp and 399Gln variants [haplotype A] had significantly higher risk of both ALL and AML. The polymorphic variants of XRCC1 codons 194 and 399 had significant unfavorable effect on disease outcome of both AML and ALL

Monocytes expressing tissue factor as a diagnostic marker for neonatal sepsis

In neonatal sepsis, several clinical and laboratory parameters have been proposed for its diagnosis, however, with variable sensitivity and specificity. The bacterial products in sepsis including endotoxin induce the production of proinflammatory cytokines that evoke the expression of tissue factor [TF] on monocytes and endothelial cells. To estimate the percentage of monocytes expressing tissue factor [TF%] by flowcytometry in patients with neonatal sepsis and to delineate its significance to diagnose neonatal sepsis. Twenty-seven neonates with neonatal sepsis and positive blood culture were recruited and evaluated clinically for their risk factors. Laboratory investigations including complete blood picture, C-reactive protein [CRP] and estimation of the monocytes TF expression by flowcytometry were done. Twenty-four normal newborns were included as a control for the laboratory data. The monocytes expressing TF% of the studied patients was significantly higher than that of the controls, p-value = 0.0001. The level of TF% was significantly influenced positively by premature rupture of membrane [PROM], Multiplicity, WBC count, staff/segment ratio, CRP and negatively by gestalional age, body weight, and platelet count. The sensitivity and overall accuracy of the TF% were higher than those of the staff/segment ratio and the WBC count for diagnosing neonatal sepsis. The areas under the receiver operating characteristic curve [AUC] of TF%, staff/segment ratio and WBC count were 0.84, 0.79 and 0.60 respectively, 95% confidence interval]. The monocytes expressing TF% is a promising diagnostic and prognostic marker of infection in neonatal sepsis with high sensitivity and overall accuracy. Adding the estimation of monocytes expressing TF% to the sepsis screen may improve the diagnosis of neonatal sepsis