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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 8 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.

Nagato L.C.,Medicine School in Sao Jose do Rio Preto FAMERP | De Souza Pinhel M.A.,Biochemistry and Molecular Biology Laboratory | De Godoy J.M.P.,Brazilian National Council for Scientific and Technological Development
Journal of Thrombosis and Thrombolysis | Year: 2012

The aim of the current study was to evaluate a possible association between apolipoprotein E (ApoE) genetic polymorphisms and deep venous thrombosis. A case-control study of ApoE genetic polymorphisms was carried out in 60 male and female patients with deep venous thrombosis and 60 male and female controls. The ages of the patients ranged between 23 and 90 years old (mean ±standard deviation: 58 ± 16.56 years) and the ages of the control group, varied between 21 and 56 years old (mean ± SD: 33 ± 10.93 years). Genetic polymorphisms were analyzed in respect to the prevalence of alleles (APOE*2, APOE*3 and APOE*4) and genotypes (APOE*2/2, APOE*2/3, APOE*2/4, APOE*3/3, APOE*3/4 and APOE*4/4). The ε2 allele was more common in patients who had suffered thrombotic events (P = 0.0034). Additionally, there was a significant difference on comparing the distribution of alleles in female patients and female controls (P = 0.027). These results demonstrate an association between the ApoE ε2 allele and deep venous thrombotic events in women. This association opens the possibility of a new line of research to better understand these thrombotic events. © Springer Science+Business Media, LLC 2011.

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.

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.
Genetics and Molecular Research | Year: 2010

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.

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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