Association between the polymorphisms of matrix metalloproteinases 9 and 3 genes and risk of myocardial infarction in Egyptian patients

The present study investigated the relationship between the genetic polymorphisms in MMP-9 and MMP-3 genes and acute myocardial infarction [AMI]. We examined 40 patients with acute myocardial infarction and 40 age and sex matched controls for MMP-9 functional promoter polymorphism [-1562 C > T] and MMP-3 [5A/6A] deletion/insertion polymorphism using restriction fragment length polymorphism [RFLP] for amplified genomic DNA. The frequencies of the combined mutant genotypes CT and TT in the [-1562 C > T] MMP9 were significantly higher in AMI patients [20%] when compared to the controls [0%] [pvalue = 0.005] showing an association between these genotypes and AMI. Also there was a significant difference between 5A/5A genotype and 5A allele frequencies when both are compared in the patients [25% and 35%] and the controls [2.5% and 18.75%] [p = 0.009; OR = 13; CI = 1.576-107.233]; and [p = 0.02; OR = 2.333, CI = 1.130-4.820] respectively. In conclusion, the -1562C > T polymorphism of the MMP9 gene is strongly associated with acute myocardial infarction in the Egyptian population. Furthermore, our study supported the presence of the 5A/5A genotype of MMP3 gene promoter polymorphism as a risk factor of AMI in Egyptian patients. Meanwhile, the race selection should be paid more attention since the pathogenesis of a disease might have different bases in different racial population groups

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

PCR and immunocytochemistry detection of p27[kip1] in chronic lymphocytic leukemia

Chronic B-cell lymphocytic leukemia [B-CLL] is a clonal expansion of B-cells with low proliferative activity in which the cells are arrested in G[0]/G[1] phase of cell cycle. p27[KIP1] is one of the KIP/CIP family of cyclin-dependent kinase inhibitors [CKIs] which inhibit all cyclin dependent kinases by direct binding to cdk complexes. It is highly expressed when cells are arrested in G[0]/G[1]and its expression declines as cells progress towards S phase. In B-CLL the non-physiological increase in p27[KIP1] appears to be of clinical relevance since high protein levels correlate with poorer survival of patients. To study the expression of p27[KIP1] in B-CLL patients and correlate these results with the clinical and laboratory data of patients. p27[KIP1] expression was determined at the mRNA level by semi-quantitative reverse transcriptase polymerase chain reaction [RT-PCR] and at the protein level by immunocytochemistry in 35 patients with de novo B-CLL and 30 healthy age- and sex-matched control subjects. p27[KIP1] mRNA levels by RT-PCR was significantly higher among CLL patients compared to the control subjects [p<0.001] and was significantly higher among group II CLL patients [lymphocyte count >30 x 10[3]/L] compared to group I CLL patients [lymphocyte count

Aberrant p15 promotor methylation in acute leukaemia

The p15 gene is one of the tumour suppressorgenes located on chromosome 9p21. In acute leukemias alterations involving the p15 gene have been reported. Commonly, these alterations involve the c[p]g islands that are commonly aberrantly methylated and result in the transcriptional loss of this gene. To detect this aberrant methylation, we used methylation specific pcr which is a novel method of pcr that can rapidly assess the methylation status of virtually any c[p]g island. The study included 30 patients: 17 cases of the novo all and 13 cases of de novo aml. Aberrant p15 gene mehylation was detected in 47.1% of cases of all and in 69.2% of casaes of AML. There was no statistically significant difference between methylated and unmethylated cases regarding the clinical and haematological data other than the peripheral blood blast cell count. On following up the patients to detect the response to therapy, there was a statistically significant difference in the response to therapy between methylated and unmethylated cases [p< 0.05]. Methylated case had a higher incidence of relapse or death [in all methylated cases 35.4% of the studied cases relapsed and 61.6% in aml patients] while the inidence of remission was 11.7% for all methylated cases and 7.7% for aml cases. Unmethylated all cases achieved remission in 41.2% of the studied group and unmethylated cases of AML reached remission in 61.6%. Aberrant p15 methylation may have important prognostic implications for clinical monitoing. And risk assessment. Also it opens new strategies of treatment using demethylating agents that can reverse this epigenetic change