Combined GSTM1 and GSTT1 null genotypes are strong risk factors for atherogenesis in a Serbian population

Oxidative stress (OS) plays an important role in atherogenesis and since glutathione S-transferases (GSTs) provide protection against OS, we have tested the hypothesis that deletion polymorphisms in two GSTs (GSTM1 and GSTT1) may affect the risk of developing atherosclerosis. A total of 382 individuals (200 patients with atherosclerosis and 182 healthy controls) were included in this association study. Genomic DNA was isolated from peripheral blood cells or from buccal epithelial cells and genotyping was performed using multiplex-PCR or real-time PCR methods. GSTM1 null genotype was significantly more frequent in atherosclerotic patients than in controls (52.0% vs 34.1%) and individuals with the GSTM1 null genotype had an approximately 2-fold increase in atherosclerosis risk (OR: 2.1, 95%CI=1.39-3.17, P=0.0004). GSTT1 null genotype alone did not show a statistically significant effect on atherosclerosis risk modulation, but the association approached significance (OR: 1.57, 95%CI=0.94-2.64, P=0.08). The combined analysis showed that the presence of both genes had a protective effect against atherosclerosis (OR=0.55, 95%CI=0.37-0.83, P=0.005) while double null genotypes led to a robust atherosclerosis risk increase (OR: 8.14, 95%CI=2.41-27.51, P lt 0.0001). This study demonstrated that the GSTM1 null and combined GSTM1/GSTT1 null genotypes are susceptibility factors for development of atherosclerosis in a Serbian population

Association between TNFRSF11B gene polymorphisms and history of ischemic stroke in Italian diabetic patients.

Osteoprotegerin (OPG) is a secretory glycoprotein that belongs to the tumor necrosis factor receptor family and plays a role in atherosclerosis. The present study aimed to evaluate whether OPG gene (TNFRSF11B) polymorphisms are involved in ischemic stroke in an Italian population with diabetes. Participants in a retrospective case-control study included 364 diabetic patients (180 males, 184 females) with history of ischemic stroke and 492 diabetic subjects without history of ischemic stroke (252 males, 240 females). The T245G, T950C, and G1181C polymorphisms of the OPG gene were analyzed by polymerase chain reaction and restriction fragment length polymorphism. We found that the T245G, T950C, and G1181C gene polymorphisms of the OPG gene were significantly (34.1 vs. 9.5 %, P < 0.0001; 30.8 vs. 6.3 %, P < 0.0001 and 26.4 vs. 11.6 % P < 0.0001, respectively) and independently (adjusted OR 5.15 [3.46-7.68], OR 6.63 [4.26-10.31], and OR 3.03 [2.04-4.50], respectively) associated with history of ischemic stroke. We also found that these three polymorphisms act synergistically in patients with stroke history. The TNFRSF11B gene polymorphisms studied are associated with history of ischemic stroke and synergistic effects between these genotypes might be potential markers for cerebrovascular disorders