Microsomal epoxide hydrolase gene polymorphisms and susceptibility to chronic obstructive pulmonary disease in the Tunisian population

It is well known that cigarette smoking is the major risk factor for chronic obstructive pulmonary disease (COPD). However, only 10%-20% of chronic heavy cigarette smokers develop symptomatic disease, which suggests the presence of genetic susceptibility. Microsomal epoxide hydrolase (EPHX1) is an enzyme involved in the protective mechanism against oxidative stress. It has been reported that gene polymorphisms of this enzyme may be associated with variations in EPHX1 activity. In this study, we aimed at investigating the relationship between EPHX1 polymorphisms and susceptibility to COPD in the Tunisian population. EPHX1 exon 3 (rs1051740, Tyr113His) and exon 4 (rs2234922, His139Arg) polymorphisms were genotyped by polymerase chain reaction followed by restriction fragment length polymorphism analysis. These techniques were used to examine a total of 416 Tunisian individuals, including 182 blood donors and a group of 234 COPD patients. All subjects were not related. An increased risk for COPD was observed in subjects with EPHX1 His113-His113 genotype (odds ratio=2.168; confidence interval 1.098-4.283; p=0.02386). However, multivariate logistic regression analysis showed no significant relationship between the mutant genotype and the disease after adjustment for sex, age, body mass index, smoking status, and pack-year smoking (odds ratio=1.524; confidence interval, 0.991-6.058; p=0.06137). Regarding the two subtypes of COPD, our investigations demonstrated that there is no significant correlation between exon 3 polymorphism and the chronic bronchitis subgroup (p=0.09034). The relation between exon 3 polymorphism and emphysema was significant in the univariate analysis (p=0.02257), but no association was found after controlling for classic risk factors (p=0.06273). In conclusion, our results showed that there is a weak relation between 113His genotype and COPD, and no apparent relation between 139Arg and COPD in the studied Tunisian population. \ua9 2010, Mary Ann Liebert, Inc

Combined analysis of EPHX1, GSTP1, GSTM1 and GSTT1 gene polymorphisms in relation to chronic obstructive pulmonary disease risk and lung function impairment

Smoking is considered as the major causal factor of chronic obstructive pulmonary disease (COPD). Nevertheless, a minority of chronic heavy cigarette smokers develops COPD. This suggests important contribution of other factors such as genetic predisposing. Our objective was to investigate combined role of EPHX1, GSTP1, M1 and T1 gene polymorphisms in COPD risk, its phenotypes and lung function impairment. Prevalence of EPHX1, GSTP1, M1 and T1 gene polymorphisms were assessed in 234 COPD patients and 182 healthy controls from Tunisia. Genotypes of EPHX1 (Tyr113His; His139Arg) and GSTP1 (Ile105Val; Ala114Val) polymorphisms were performed by PCR-RFLP, while the deletion in GSTM1 and GSTT1 genes was determined using multiplex PCR. Analysis of combinations showed a significant association of 113His/His EPHX1/null-GSTM1 (OR=4.07) and null-GSTM1/105Val/Val GSTP1 (OR =3.56) genotypes with increased risk of COPD (respectively P=0.0094 and P=0.0153). The null-GSTM1/ null-GSTT1, 105Val/Val GSTP1/null GSTT1, 113His/His EPHX1/null-GSTM1 and null-GSTM1/105Val/Val GSTP1 genotypes were related to emphysema (respectively P=0.01; P=0.009; P=0.008 and P=0.001). Combination of 113His/His EPHX1/null-GSTM1 genotypes showed a significant association with the decrease of Δ FEV1 in patients (P =0.028). In conclusion, our results suggest combined EPHX1, GSTP1, GSTM1 and GSTT1 genetic polymorphisms may play a significant role in the development of COPD, emphysema and decline of the lung function. \ua9 2011 - IOS Press and the authors. All rights reserved

Hemoglobinopathies in North Africa: a review.

International audienc

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 involve-ment of various environmental factors. Several candidate genes have been reported as potentially associated with this lung disease. The glu-tathione 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 car-cinogens, therapeutic drugs, environmental toxins, and oxidative stress products. We conducted a case-control study to investigate genetic poly-morphisms 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 com-mon in patients compared to controls (OR = 2.67; 95%CI = 1.45-4.92; P = 0.0013). Multivariate logistic regression analysis confirmed a signifi-cant 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 in-dex, 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

Oxidative stress and COPD: Polymorphism of glutathione S-transferase and contribution of clinical phytotherapy / Le stress oxydatif et la BPCO: Polymorphisme des glutathion- stransf\ue9rases et apport de la phytoth\ue9rapie clinique

The oxidative stress is incriminated as cause or consequence of numerous pathologies such as, the inflammatory syndromes, cancer, diabetes, as well as in chronic obstructive pulmonary disease (COPD). Researches were developed on the biological, clinical and molecular exploration of COPD. This pathology is characterized by an airflow limitation that is not fully reversible. Consequently, we attend an important back keeping of numerous environmental toxins in the respiratory system. The measures of personal exposure to tobacco smoke, dusts and professional chemicals, as well as internal and external air pollutants reduction are important objectives in the primary and secondary prevention of CPOD. The system purifying oxidative stress is complex. It includes enzymatic and non-enzymatic ways. Among the enzymatic families, the glutathione-S-transferases constitute an important agent of detoxification. The analysis of polymorphisms of genes coding these proteins was undertaken in the perspective of the research for a positive correlation with the oxidative stress. In COPD patients sample followed in hospitals of Central Tunisia, we detected an association of genotypes null-allele GSTM1 (p=0,02) and Val105/Val105 GSTP1 (p=0,001) with the development of the pathology. Besides in the prospect to contribute to the preventive efforts and to the improvement of the therapeutic solutions, we led an investigation with the followers of the clinical herbal medicine. Some plants facilitate the hepatic detoxification and several species are recommended for that purpose. We distinguish plants with vitamins and rich in trace elements (roots of Daucus carota, fruits of Rosa canina). We also privilege plants to active antioxidant principles as the ginkgo (ginkgolides, bilobalides), the thistle marries Silybum marianum (sylimarine) and even green tea (epigallocatechines)

Alpha 1 antitrypsin polymorphism associated to asthma and emphysema in a central Tunisian population

International audienc

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

International audienc

Association of GSTM1 and GSTT1 polymorphisms with chronic obstructive pulmonary disease in a Tunisian population.

International audienceGSTM1 and GSTT1 polymorphisms have been proposed in relationship with chronic obstructive pulmonary disease (COPD). We investigated the association between these polymorphisms and COPD (as well as its subtypes emphysema and chronic bronchitis) in 234 COPD patients and 182 healthy controls in the Tunisian population. Genotyping was performed using multiplex PCR. GSTM1-null genotype frequency was significantly higher in COPD patients than in controls (P = 0.02); however, multivariate analysis of cofounding variables showed no independent association with this genotype (P = 0.073). In contrast, the association of the GSTM1-null genotype with emphysema was significant, even after adjustment for risk factors (P = 0.011). There were no significant differences in GSTT1 genotypes between patients and controls. The GSTM1 null allele is likely not an independent risk factor for COPD but is related to emphysema, whereas the GSTT1 gene is not associated with the disease

Association of <em>GSTM1</em> and <em>GSTT1</em> polymorphisms with chronic obstructive pulmonary disease in a Tunisian population

GSTM1 and GSTT1 polymorphisms have been proposed in relationship with chronic obstructive pulmonary disease (COPD). We investigated the association between these polymorphisms and COPD (as well as its subtypes emphysema and chronic bronchitis) in 234 COPD patients and 182 healthy controls in the Tunisian population. Genotyping was performed using multiplex PCR. GSTM1-null genotype frequency was significantly higher in COPD patients than in controls (P = 0.02); however, multivariate analysis of cofounding variables showed no independent association with this genotype (P = 0.073). In contrast, the association of the GSTM1-null genotype with emphysema was significant, even after adjustment for risk factors (P = 0.011). There were no significant differences in GSTT1 genotypes between patients and controls. The GSTM1 null allele is likely not an independent risk factor for COPD but is related to emphysema, whereas the GSTT1 gene is not associated with the disease. \ua9 2010 Springer Science+Business Media, LLC