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ABSTRACT. Glutathione S-transferase (GST) protects cells against oxidative stress. We evaluated the effect of genetic polymorphisms of the GST gene family on the risk of developing type-2 diabetes mellitus and on glycemic control. We also investigated the effects of smoking combined with these polymorphisms on type-2 diabetes mellitus risk. We enrolled 100 type-2 diabetes mellitus patients and 100 healthy controls matched for age, gender and origin, from the Sinai area of Egypt. Fasting serum glucose, HbA 1c and lipid profiles were determined. Two polymorphisms were identified by multiplex PCR within the GST genes: GSTM1 and GSTT1. The proportion of the GSTT1-and GSTM1-null genotypes was significantly greater in diabetic patients when compared to controls. Patients carrying both null polymorphisms had a 3.17-fold increased risk of having type-2 diabetes mellitus compared to those with normal genotypes of these two genes (P = 0.009). Additionally, patients with the GSTT1-null genotype had higher levels of triglycerides and very low-density lipoprotein cholesterol compared to those with the ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 10 (4): 3722-3730 (2011) Influence of GST polymorphisms on type-2 DM risk 3723 GSTT1-present genotype. On the other hand, patients with the GSTM1-null genotype had significantly higher levels of HbA 1c and significantly higher diastolic blood pressure compared to those with the GSTM1-present genotype. The interaction between these genotypes and smoking status was not significant. These results give evidence that the GSTT1-and GSTM1-null genotypes, alone or combined, are associated with increased risk of type-2 diabetes mellitus, regardless of smoking status.Only the GSTM1-null genotype had an effect on glycemic control.

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IntroductionType 2 diabetes mellitus (T2DM) is associated with increased production of reactive oxygen species and a reduction in antioxidant defenses leading to oxidative stress. Glutathione S-transferases (GSTs) modulate oxidative stress. The present cross-sectional study was aimed at investigating the association between the GSTP1 gene polymorphism and T2DM and to clarify their effect on the glycemic control parameters.Material and methodsFrom the Egyptian population, we enrolled 112 T2DM patients and 188 healthy controls matched for age, sex and origin. Serum lipid profile, blood-glucose level, glycated hemoglobin (HbA1c) and body mass index (BMI) were measured. DNA was extracted from the blood samples. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to measure GSTP1 Ile105Val gene polymorphism of study participants.ResultsThe frequency of the Val allele in exon 5 of the GSTP1 gene in patients with T2DM was higher than that observed in healthy controls (15.2% vs. 9.6%); the difference was considered statistically significant when compared to Ile allele carriers (p = 0.03). The presence of the GSTP1 heterozygous mutant allele Ile/Val was more common in subjects with T2DM than in the control group (30.4% and 19.2%, respectively; p = 0.02). Variation in the GSTP1 gene was associated with BMI (p = 0.02) and not associated with glycemic control parameters (fasting serum glucose and HbA1c) or smoking-related risk of T2DM.ConclusionsGSTP1 gene polymorphism may play a significant role in increasing the susceptibility to and risk of T2DM and obesity regardless of smoking status and had no apparent effect on HbA1c in patients with diabetes mellitus.

Red Sea sponges offer potential as sources of novel drugs and bioactive compounds. Sponges harbor diverse and abundant prokaryotic communities. The diversity of Egyptian sponge-associated bacterial communities has not yet been explored. Our study is the first culture-based and culture-independent investigation of the total bacterial assemblages associated with two Red Sea Demosponges, Hyrtios erectus and Amphimedon sp. Denaturing gradient gel electrophoresis fingerprint-based analysis revealed statistically different banding patterns of the bacterial communities of the studied sponges with H. erectus having the greater diversity. 16S rRNA clone libraries of both sponges revealed diverse and complex bacterial assemblages represented by ten phyla for H. erectus and five phyla for Amphimedon sp. The bacterial community associated with H. erectus was dominated by Deltaproteobacteria. Clones affiliated with Gammaproteobacteria were the major component of the clone library of Amphimedon sp. About a third of the 16S rRNA gene sequences in these communities were derived from bacteria that are novel at least at the species level. Although the overall bacterial communities were significantly different, some bacterial groups, including members of Alphaproteobacteria, Gammaproteobacteria, Acidobacteria, and Actinobacteria, were found in both sponge species. The culture-based component of this study targeted Actinobacteria and resulted in the isolation of 35 sponge-associated microbes. The current study lays the groundwork for future studies of the role of these diverse microbes in the ecology, evolution, and development of marine sponges. In addition, our work provides an excellent resource of several candidate bacteria for production of novel pharmaceutically important compounds.