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Mahdia, Tunisia

Denden S.,Biochemistry and Molecular Biology Laboratory | Denden S.,Tunis el Manar University | Lakhdar R.,Biochemistry and Molecular Biology Laboratory | Boudawara Keskes N.,CHU Tahar Sfar | And 3 more authors.
Biochemical Genetics | Year: 2013

It is generally agreed that the protease inhibitor (PI) alleles PI S (Val264Glu) and PI Z (Lys342Glu) are the most common alpha 1 antitrypsin deficiency variants worldwide, but the PI Mmalton allele (ΔPhe52) prevails over these variants in some Mediterranean regions. In eastern Tunisia (Mahdia), we screened 100 subjects with chronic obstructive pulmonary disease for these variants. The PI S and PI Z alleles were genotyped by the previously described SexAI/Hpγ99I RFLP-PCR. We provide here a new method for PI Mmalton genotyping using mismatched RFLP-PCR. These methods are suitable for routine clinical application and can easily be reproduced by several laboratories, since they do not require extensive optimization, unlike the previously described bidirectional allele-specific amplification PCR for PI Mmalton genotyping. Our results were in agreement with previous reports from central Tunisia (Kairouan), suggesting that the PI Mmalton mutation is the most frequent alpha 1 antitrypsin deficiency-related mutation in Tunisia. © 2013 Springer Science+Business Media New York.


Lakhdar R.,Biochemistry and Molecular Biology Laboratory | Denden S.,Biochemistry and Molecular Biology Laboratory | Mouhamed M.H.,Biochemistry Laboratory | Chalgoum A.,Biochemistry Laboratory | And 6 more authors.
Experimental Lung Research | Year: 2011

This study was undertaken to ascertain if a relationship existed between oxidative status and polymorphisms of microsomal epoxide hydrolase X1 (EPHX1), glutathione S-transferase P1 (GSTP1), GSTM1, and GSTT1 in chronic obstructive pulmonary disease (COPD). Erythrocyte glutathione peroxidase (GSH-px), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), and plasma GST activities and total antioxidant status (TAS) as antioxidative stress markers were determined and compared either with individual and combined genotypes of EPHX1 exon 3, GSTP1 exon 5, GSTM1, and GSTT1 polymorphisms in COPD patients and healthy controls from the central area of Tunisia. Statistical data processing revealed significantly lower GSH-px, GR, SOD, CAT, GST, and TAS values in COPD patients in comparison to the control group (P <.001). As for genotypes, there was a no significant association in each of the 6 parameters and individual genotypes (P >.05). A significant correlation between the studied parameters and combined null GSTM1/null GSTT1 (GSH-px: P <.001, GR: P =.026, CAT: P =.018, GST: P =.022, TAS: P =.046), His113His EPHX1/null GSTM1 (GSH-px: P =.001, GST: P =.0012, TAS: P =.013), His113His EPHX1/Val105Val GSTP1 (GSH-px: P =.048, CAT: P =.026, GST: P =.031), and null GSTM1/Val105Val GSTP1 (GSH-px: P =.011, GR: P =.0028, GST: P =.0054, TAS: P =.032) was found in patients. In conclusion, combined genetic polymorphisms of GSTM1, GSTT1, GSTP1, and EPHX1 may have favorable effects on redox balance in COPD patients. © 2011 Informa Healthcare USA, Inc.


Denden S.,Biochemistry and Molecular Biology Laboratory | Khelil A.H.,Biochemistry and Molecular Biology Laboratory | Knani J.,CHU Tahar Sfar | Lakhdar R.,Biochemistry and Molecular Biology Laboratory | And 3 more authors.
Genetics and Molecular Biology | Year: 2010

Alpha-1-antitrypsin (AAT) plays an important role in the pathogenesis of emphysema, the pathological lesion underlying the majority of the manifestations of Chronic Obstructive Pulmonary Disease (COPD). In this study we tested the hypothesis that common AAT polymorphisms influence the risk of developing COPDs. We investigated PiM1 (Ala213Val), PiM2 (Arg101His), PiM3 (Glu376Asp), PiS (Glu264Val) and PiZ (Glu342Lys) SERPINA1alleles in 100 COPD patients and 200 healthy controls. No significant differences were observed in allele frequencies between COPD patients and controls, neither did haplotype analysis show significant differences between the two groups. A cross-sectional study revealed no significant relationship between common SERPINA1 polymorphisms (PiM1, PiM2, PiM3) and the emphysematous type of COPD. In addition, FEV1 annual decline, determined during a two-year follow up period, revealed no difference among carriers of the tested polymorphisms. Copyright © 2009, Sociedade Brasileira de Genética.


Lakhdar R.,University of Monastir | Denden S.,University of Monastir | Knani J.,CHU Tahar Sfar | Leban N.,University of Monastir | And 5 more authors.
Biochemical Genetics | Year: 2010

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. © 2010 Springer Science+Business Media, LLC.


Lakhdar R.,Biochemistry and Molecular Biology Laboratory | Denden S.,Biochemistry and Molecular Biology Laboratory | Knani J.,CHU Tahar Sfar | Leban N.,Biochemistry and Molecular Biology Laboratory | And 5 more authors.
Disease Markers | Year: 2011

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. © 2011 - IOS Press and the authors. All rights reserved.

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