Relationship between glutathione S-transferase P1 polymorphisms and chronic obstructive pulmonary disease in a Tunisian population.

Chronic obstructive pulmonary disease (COPD) is a multifactorial disease with possible genetic predisposition and involvement of various environmental factors. Several candidate genes have been reported as potentially associated with this lung disease. The glutathione S-transferase P1 gene (GSTP1) was proposed to be involved in susceptibility to develop COPD. It belongs to the GST family, which is a group of phase II enzymes that catalyze the glutathione conjugation of many endogenous and exogenous electrophilic compounds, such as carcinogens, therapeutic drugs, environmental toxins, and oxidative stress products. We conducted a case-control study to investigate genetic polymorphisms of this enzyme [exon 5 (Ile105Val) and exon 6 (Ala114Val)] in 234 unrelated COPD cases and 182 healthy controls from a Tunisian population. Genotyping was carried out using polymerase chain reaction and restriction fragment length polymorphism methods. GSTP1 Ala114/Val114 and Val114/Val114 genotypes were not found in either patients or healthy controls. However, there were differences in the distribution of various exon 5 GSTP1 genotypes between COPD patients and healthy controls. GSTP1 Val105/Val105 was significantly more common in patients compared to controls (OR = 2.67; 95%CI = 1.45-4.92; P = 0.0013). Multivariate logistic regression analysis confirmed a significant relationship between the mutant genotype and COPD (OR = 2.58; 95%CI = 1.31-5.09; P = 0.026), after adjustment for classic risk factors. Analysis of variance showed no correlation between age, body-mass index, pack-years, percentage of predicted FEV1 values, and any of the GSTP1 genotypes. We conclude that subjects with GSTP1 Val105 allele are at higher risk of COPD.

[Oxidant stress and cardiovascular absolute risk in Tunisian type 2 diabetes]. / Stress oxydant et risque cardiovasculaire absolu chez des diabétiques de type 2 du centre tunisien.

INTRODUCTION: cardiovascular diseases constitute the most hefty complications in diabetes. Absolute cardiovascular risk (ACVR) can be estimated by many equations that are continuously criticised. The aim is, in one hand, to evaluate ACVR in type 2 diabetes and, in the other hand, is to establish correlations between ACVR and oxidant-antioxidant status. MATERIAL AND METHODS: 183 type 2 diabetes and 200 controls were admitted. ACVR assessment was calculated following Laurier equation. Oxidant status was evaluated by the measure of homocysteine, hydrogen peroxide (H2O2) and LDL thiobarbituric reactive oxygen substances (LDL-TBARS). Antioxidant status was evaluated by the measure of superoxide dismutase (SOD) activity, glutathione peroxidase (GPx), total antioxidant status (TAS) vitamins A, E and zinc. Glycated haemoglobin (HbA1c) and microalbuminuria were assessed by turbidimetry. RESULTS: ninety percent of diabetes belonged to moderate and high ACVR groups. In diabetic men ACVR was doubled each elevation of 4 micromol/L homocysteine, of 50 micromol/L of H2O2 and of 20 mg/L of microalbuminuria. High risk ACVR group showed the lowest SOD activity, zincemia and the highest HbA1c. No significant difference was found in LDL-TBARS, TAS, GPx, vitamins A, E between the different ACVR groups. The strong relation between homocysteine and ACVR confirms homocysteine atherosclerotic role. Homocysteine auto-oxidation produces H2O2 leading to LDL-TBARS increase. Microalbuminuria-ACVR association verifies its vasculopathy predictor role. Urinary albumin leakage may be consequent to the hyperhomocysteinemia found in diabetes. CONCLUSION: homocysteine introduction in ACVR assessment equation may ameliorate this estimation.

Alpha 1 antitrypsin polymorphism in the Tunisian population with special reference to pulmonary disease.

OBJECTIVES: The study investigated alpha 1 antitrypsin (AAT) gene polymorphism in the Tunisian population. We aimed to analyze the correlation between Pi polymorphism and the risk of developing chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: We focused our study on two samples originating from the Tunisian centre: 318 healthy controls and 90 patients suffering from COPD. Data analysis was investigated by AAT level quantification, serum isoelectric focusing (IEF) and RFLP-PCR performed with PiS and PiZ allele specific primers. RESULTS: We calculated PiM1, PiM2, PiM3, PiS and PiZ allele frequencies in patients and controls. The difference in allele frequencies is significant only for the PiM2 allele (P=0.00378). In COPD patients, we note the presence of PiZ allele. This allele mainly observed in European populations, is rare in sub-Saharian populations and not described in North Africa. CONCLUSION: PiZ allele is found in COPD sample and never in Tunisian controls. However, no significant difference in PiZ allele frequency between patients and controls can be concluded. PiM2 allele, which is considered as "normal" variant can be associated with COPD risk.