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

Tumor necrosis factor-alpha, interleukin-4 and interleukin-6 levels in tears of patients with keratoconus

To detect levels of interleukin-4 [IL-4]. Interleukin-6 [IL-6] and tumor necrosis factor-alpha [TNF-alpha] in tears of patients with keratoconus arid their relation to the disease severity. Eighteen patients diagnosed with keratoconus and 6 control subjects with no clinical or topographic evidence of keratoconus were included. History of allergy and eye rubbing was documented. Patients were classified into early and advanced keratoconus according to the steep keratometric reading [K2]. Thirty microliters of tears were collected by capillary flow from the lower fornix of the right eye of each patient and control subject without nasal stimulation. Levels of [IL-4] [IL-6], [TNF-alpha] were determined by competitive enzyme immunoassay [IL-4 and IL-6] and by enzyme amplified sensitivity immunoassay [TNF-alpha]. Patients with keratoconus had a significantly high levels of Both IL-6 [7.67 +/- 1.83 pg/ml] versus the control group [3.02 +/- 1.04 pg/mL] p<0.001 and TNF-alpha [55.12 +/- 13.68 pg/mL] versus the control group [45.20 +/- 6.26 pg/mL p<0.05. Among keratoconus patients, the level of cytokines was significantly increased in advanced then early keratoconus. There was no statistically significant difference between cytokine levels in patients with and without allergic manifestations. High levels of IL-6 and TNF-alpha are expressed in tears of patients with keratoeonus, IL-4 expression is also increased in advanced disease. These findings propose a possible inflammatory etiology for keratoconus

Clinical implications of markers of apoptosis in patients with myocardial infarction

To examine the possible participation of the Fas/Fas ligand [Fas-L] system and tumor necrosis factor-alpha [TNF-alpha] in the pathogenesis of acute and old myocardial infarction [AMI and OMI] in a trial to explore the role of immune mechanisms in the pathogenesis of these conditions. Serum levels of sFas, sFasL and TNF-alpha were measured in 10 patients with AMI, 12 patients with OMI and 15 normal subjects as control group. We excluded AMI patients with congestive heart failure, concomitant inflammatory disease, cancer or other significant heart diseases. Serum levels of sFas, sFas ligand and TNF-a were determined by ELISA. Serum levels of sFas and TNF-alpha were greater than normal only in patients with AMI compared to normal subjects, however, there was no difference among serum levels of sFasL for all groups. We found that circulating levels of sFas and TNF-alpha in patients with AMI increase during the early phase of disease whereas levels of sFas ligand remained unchanged. Therefore circulating sFas and TNF-a could play an important role as marker of pathophysiologic conditions associated with cardiomyocyte apoptosis in AMI