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Puechal X.,systemIC | Puechal X.,University of Paris Descartes | Bienvenu T.,Biochemistry and Molecular Biology Laboratory | Genin E.,French Institute of Health and Medical Research | And 9 more authors.
Annals of the Rheumatic Diseases | Year: 2011

Objectives: In cystic fibrosis, mutations of the CFTR gene lead to diffuse bronchiectasis (DB). DB is also associated with other diseases including rheumatoid arthritis (RA) in which the role of genetic factors in the predisposition to DB remains unclear. Methods: A family-based association study was carried out to determine whether the frequency of CFTR mutations was higher in patients with RA-associated DB and to determine whether a causal relationship could be established between the variant and the disease by evaluating its cosegregation with DB within families. Families of probands with RA-DB were included if one first-degree relative had RA and/or DB. The controls comprised healthy subjects requesting genetic counselling because their partner had cystic fibrosis. Results: The frequency of CFTR mutations was higher in family members with RA-DB or DB only than in unaffected relatives (p<0.005 for each comparison) and in unrelated healthy controls (p<0.001 for each comparison) but not in family members with RA only. CFTR mutations were more frequent in family members with RA-DB than in those with RA only (OR 5.30, 95% CI 2.48 to 11.33; p<5×10-5). They cosegregated with RA-DB in the families (sib-TDT=10.82, p=0.005). Conclusions: RA-DB should be added to the list of phenotypes in which CFTR mutations are pathogenic. CFTR mutation is the first genetic defect linked to an extra-articular feature of RA to be described. CFTR mutations in patients with RA appear to be an important marker of the risk of associated DB, which has been linked to a less favourable prognosis.


Duarte A.M.R.C.,Biochemistry and Molecular Biology Laboratory | Pereira D.M.,Biochemistry and Molecular Biology Laboratory | De Paula M.B.,University of Sao Paulo | Fernandes A.,University of Sao Paulo | And 8 more authors.
Parasites and Vectors | Year: 2013

Background: A descriptive study was carried out in an area of the Atlantic Forest with autochthonous malaria in the Parelheiros subdistrict on the periphery of the municipality of São Paulo to identify anopheline fauna and anophelines naturally infected with Plasmodium as well as to discuss their role in this peculiar epidemiological context. Methods. Entomological captures were made from May 2009 to April 2011 using Shannon traps and automatic CDC traps in four areas chosen for their different patterns of human presence and incidences of malaria (anthropic zone 1, anthropic zone 2, transition zone and sylvatic zone). Natural Plasmodium infection was detected by nested PCR based on amplification of the 18S rRNA gene. Results: In total, 6,073 anophelines were collected from May 2009 to April 2011, and six species were identified in the four zones. Anopheles cruzii was the predominant species in the three environments but was more abundant in the sylvatic zone. Anopheles (Kerteszia) cruzii specimens from the anthropic and sylvatic zones were positive for P. vivax and P. malariae. An. (Ker.) bellator, An. (Nys.) triannulatus, An. (Nys.) strodei, An. (Nys.) lutzi and An. (Ano) maculipes were found in small numbers. Of these, An. (Nys.) triannulatus and An. (Nys.) lutzi, which were collected in the anthropic zone, were naturally infected with P. vivax while An. (Nys.) triannulatus from the anthropic zones and An. (Nys.) strodei from the transition zone were positive for P. malariae. Conclusion: These results confirm that Anopheles (Kerteszia) cruzii plays an important role as a major Plasmodium vector. However, the finding of other naturally infected species may indicate that secondary vectors are also involved in the transmission of malaria in the study areas. These findings can be expected to help in the implementation of new measures to control autochthonous malaria in areas of the Atlantic Forest. © 2013 Duarte et al.; licensee BioMed Central Ltd.


PubMed | French Institute of Health and Medical Research, CHU Fattouma Bourguiba, Higher Institute of Biotechnology of Monastir and Biochemistry and Molecular Biology Laboratory
Type: | Journal: Pigment cell & melanoma research | Year: 2016

Vitiligo and Alopecia areata (AA) are autoimmune T cell-mediated diseases of the skin that share the implication of the IFN pathway in their pathophysiology. C-X-C motif chemokine receptor 3 (CXCR3) and its ligands, C-X-C motif chemokine ligand 9 (CXCL9), CXCL10 and CXCL11, are linked to the Th1 pattern and have been suggested as one of the most relevant chemokine axes that promote T cell migration in different autoimmune and inflammatory processes (Lacotte etal., 2009). Chemokines play an important role in regulating the homing of immune cells (Vazirinejad etal., 2014). This article is protected by copyright. All rights reserved.


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.


Lakhdar R.,Biochemistry and Molecular Biology Laboratory | Denden S.,Biochemistry and Molecular Biology Laboratory | Kassab A.,Biochemistry Laboratory | Leban N.,Biochemistry and Molecular Biology Laboratory | And 5 more authors.
Experimental Lung Research | Year: 2011

Chronic obstructive pulmonary disease (COPD) is characterized by systemic and local chronic inflammation and oxidative stress. The sources of the increased oxidative stress in COPD patients derive from the increased burden of inhaled oxidants such as cigarette smoke and other forms of particulate or gaseous air pollution and from the increase in reactive oxygen species (ROS) generated by several inflammatory, immune, and structural airways cells. There is increasing evidence that genetic factors may also contribute to the pathogenesis if COPD, particularly antioxidant genes, which may confer a susceptibility to environmental insults such as cigarette smoke and thereafter development of COPD. Consequently, heme oxygenase-1 (HO-1), superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), microsomal epoxide hydrolase (EPHX1), and cytochrome P450 (CYP) genetic polymorphisms may have an important role in COPD pathogenesis. In this review the authors summarized the most recent findings dealing with these antioxidant genes contributing to the free radical neutralization and xenobiotic enzymes playing a role in different phases of cell detoxification reactions related to the redox status imbalance in COPD, with an emphasis on their possible roles in disease progression. © 2011 Informa Healthcare USA, Inc.


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 | 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.


Denden S.,Biochemistry and Molecular Biology Laboratory | Lakhdar R.,Biochemistry and Molecular Biology Laboratory | Leban N.,Biochemistry and Molecular Biology Laboratory | Ben Chibani J.,Biochemistry and Molecular Biology Laboratory | Haj Khelil A.,Biochemistry and Molecular Biology Laboratory
Molecular Biotechnology | Year: 2010

Alpha 1 antitrypsin deficiency (AATD) is a well recognized genetic risk factor for pulmonary disease and less common liver disease. The two most common deficiency alleles worldwide PI*S and PI*Z can be easily detected using several molecular methods. However, there are at least 30 other AATD variants, which are only detectable by alpha 1 antitrypsin (AAT) gene sequencing and, therefore, seem to be more under-recognized than the PI*S and PI*Z alleles. PI*Mmalton is the most frequent AATD variant in different regions of the Southern Mediterranean basin countries, where its prevalence seems to prevail over PI*S and PI*Z. In this work, we report the development of a simple PCR-based analysis designed for the detection of the PI*Mmalton deficiency alleles using two specific primers. A one-tube reaction enables the distinction between the different genotypes. This reliable, easy, fast, and low-cost technique might be useful for laboratories involved in the study of AATD-related diseases, especially those of the Southern Mediterranean basin area with modest budget or where sophisticated equipment is not available. This will allow larger targeted screening for PI*Mmalton in order to better understand this mutation epidemiology and its origin. © Springer Science+Business Media, LLC 2010.


PubMed | Biochemistry and Molecular Biology Laboratory
Type: | Journal: Parasites & vectors | Year: 2013

A descriptive study was carried out in an area of the Atlantic Forest with autochthonous malaria in the Parelheiros subdistrict on the periphery of the municipality of So Paulo to identify anopheline fauna and anophelines naturally infected with Plasmodium as well as to discuss their role in this peculiar epidemiological context.Entomological captures were made from May 2009 to April 2011 using Shannon traps and automatic CDC traps in four areas chosen for their different patterns of human presence and incidences of malaria (anthropic zone 1, anthropic zone 2, transition zone and sylvatic zone). Natural Plasmodium infection was detected by nested PCR based on amplification of the 18S rRNA gene.In total, 6,073 anophelines were collected from May 2009 to April 2011, and six species were identified in the four zones. Anopheles cruzii was the predominant species in the three environments but was more abundant in the sylvatic zone. Anopheles (Kerteszia) cruzii specimens from the anthropic and sylvatic zones were positive for P. vivax and P. malariae. An. (Ker.) bellator, An. (Nys.) triannulatus, An. (Nys.) strodei, An. (Nys.) lutzi and An. (Ano) maculipes were found in small numbers. Of these, An. (Nys.) triannulatus and An. (Nys.) lutzi, which were collected in the anthropic zone, were naturally infected with P. vivax while An. (Nys.) triannulatus from the anthropic zones and An. (Nys.) strodei from the transition zone were positive for P. malariae.These results confirm that Anopheles (Kerteszia) cruzii plays an important role as a major Plasmodium vector. However, the finding of other naturally infected species may indicate that secondary vectors are also involved in the transmission of malaria in the study areas. These findings can be expected to help in the implementation of new measures to control autochthonous malaria in areas of the Atlantic Forest.


PubMed | Biochemistry and Molecular Biology Laboratory
Type: | Journal: Diagnostic pathology | Year: 2014

Myocardial infarction (MI) is a major clinical problem because of its large contribution to mortality. The genetic bases of this disease have been widely studied in recent years to find a clear association with some genetic markers that increase the risk of its occurrence. In the present investigation, the correlation between MI and the C3 complement polymorphism was analyzed using a case-control study.Our study ported on one hundred seventy survived myocardial infarction patients and ninety five healthy controls. The C3 allele identification was investigated using the amplification refractory mutation system PCR to determine the C3*S and the C3*F alleles of the C3 polymorphism.Frequencies of C3*S and C3*F in patients are 0.59 and 0.41 respectively. Fisher test results showed a significant increase of C3*F allele in the sample of patients (0.41; odds ratio: 2.616; C.I [1.738-3.938]) compared to controls (0.21; odds ratio: 0.382; 95% CI [0.254-0.575]), p=2.742 10-6.A strong positive correlation was found between C3 polymorphism and MI estimating that the risk of myocardial infarction is significantly increased among patients with C3*F allele of this polymorphism.The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1190484203893646.

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