Association of type 2 diabetes mellitus and glutathione S transferase [GSTM1 and GSTT1] genetic polymorphism

Oxidative stress, arising as a result of an imbalance between free radicals and anti-oxidant defenses, is associated with damage to lipids, proteins and nucleic acids, which could contribute to cellular dysfunctions leading to the pathophysiology of various diseases including atherosclerosis, Lancer and diabetes mellitus. Glutathione S-transferases [GSTs] belong to a group of multigene and multifunctional doioxification enzymes, which defend cells against a wide variety of toxic insults. An important condition affecting GST expression is oxidative stress, usually observed in diabetes. To assess whether the glutathione S-transferase T1 [GSTT1] and M1[GSTM1] genotypes are associated with type 2 diabetes mellitus and to ascertain whether the levels of blood lipids given exposure to diabetes are modified by the specific genetic polymorphisms of GSTT1 and GSTM1. Using a multiplex polymerase chain reaction, GSTT1 and GSTM1 gene polymorphisms were analyzed in 29 patients with type 2 diabetes mellitus compared to 16 healthy age and sex matched control group. The association between genotypes and blood lipids were assessed separately for all the study subjects [type 2 diabetes mellilus group and the control group] with GSTT1 null and also for GSTM1 null compared to GSTT1 present and GSTM1 present genotypes respectively. The proportion of GSTT1 null genotypes was higher in diabetic patients as compared to controls [17.24% versus 6.25%]. No significant difference of the frequency of GSTM1 null was observed between cases and controls [58.6% versus 62.5%]. The GSTT1 present genotype conferred a statistically significant 0.39 fold reduction in risk of type 2 diabetes mellitus relative to the null genotype of the GSTT1 genotype but the GSTM 1 genotype did not differ with respect to their association with risk of type 2 diabetes mellitus. Among individuals with GSTT1 null and GSTM1 null, the serum cholesterol, triglycerides and high density lipoprotein were not significantly different from GSTT1 present or GSTM 1 present genotypes. GSTT1 gene polymorphisms may play an important role in type 2 diabetes mellitus pathogenesis. The potential role of GSTM1 polymorphism as a marker of susceptibility to type 2 diabetes mellitus needs further studies in a larger number of patients. GSTT1 and GSTM1 null genotype do not have an effect on blood lipids

Patterns of 5q allelic imbalance in bladder cancer

In Egypt, urinary bladder cancer [BC] is still a major health problem. The frequency of BC accounts for 31% of all cancers [39% and 11% of cancers in males and females, respectively]. A causal relationship between BC and schistosomiasis has been proposed since 1911, where Egypt is considered a hyperendemic area of schistosome infection. A notable cytogenetic finding in a comparative genomic hybridization [CGH] study on Egyptian BC cases entailed the prevalent loss of long arm of chromosome 5 [5q] in squamous cell carcinoma [SCC] in comparison to other BC subtypes. The current work aimed to assess the relative importance of Sq loss and imbalance in BC among Egyptian patients, using polymorphic microsatellite analysis. Genomic DNA was extracted from tumorous bladder tissues as well as from whole blood of 31 Egyptian BC cases. The polymerase chain reaction [PCR] was employed to amplify four tetranucleotide repeats, D5S1393, D5S818, D5S816 and D5S1392 which are located on the 5q regions 14.3, 23.1, 31.1, and 34 respectively. A number of findings were noted, despite not reaching statistical significance. First, 5q 14.3 Al prevailed in Schistosomal BC [8/19] in comparison to nonschistosomal one [1/7]. Second, only grade H tumors showed allelic imbalance in 5q14.3 and 5q31.1 [9/16 and 7/16, respectively]. Third, there were some gender- related differences in rates of AT in 5q23.1 and 5q34. Forth, no Al could be detected in only 8 tumors [7 SCC and 1 TCC] out of 31[26%]. In conclusion, the current study presents evidence of the importance of 5q Al among BC patients. Allelic imbalance entails more than one suggested mechanism, i.e. allelic loss pointing to the presence of relevant putative tumor suppressor gene[s] in the area. In addition, other mechanisms of allelic imbalance involve microsatellite instability caused by errors in DNA replication. It is uncertain how these DNA replicative errors generate mutations that provide a survival advantage resulting in clonal expansion

Allele profiles of short tandem repeat loci in Egyptians

In this study, relative allele frequencies of 4 short tandem repeats [STR] loci in 47 unrelated subjects from Egyptian population as a primary step for forming a nationwide database was reported. The sample represented various geographical, ethnic and religious backgrounds that constituted contemporary Egyptian population. DNA was extracted from whole blood using salting out method. The allele patterns in Egyptian sample showed high levels of heterozygosity over 74% in 3 loci. The interpopulation differences were least detected with Caucasians and most with Asian and Hispanic Americans