J. Ben Chibani

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.

CRP relevance in clinical assessment of chronic spontaneous urticaria Tunisian patients

Abstract Background: Chronic spontaneous urticaria (CSU) is a common dermatological condition defined by the sudden occurrence of daily wheals and pruritus for at least six weeks. Multifactorial origin is suggested such as oxidative stress. This latter may play a double role as a trigger and remnant agent. Objectives: The first aim of this study is to investigate antioxidant status, inflammatory proteins, hematologic counts and clinical assessment in CSU patients. The second aim is to evaluate the effect of a first-line treatment: desloratadine 5 mg/d on these different parameters. Patients and Methods: This study enrolled 30 CSU patients and same number of controls. We assessed the urticaria activity score (UAS), total antioxidant status (TAS), glutathione S-transferase (GST), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), albumin, alpha1, alpha2, beta1 beta2, gamma globulins, c-reactive protein (CRP) and hematologic numeration. Results: At baseline alpha1, alpha2, beta1, beta2, gamma globulins, CRP, SOD activity, leukocytes and basophils were significantly higher in patients versus controls (p < 0.05). TAS, GST, CAT, GPx and albumin were significantly low in patients versus controls (p < 0.05). After treatment, TAS, GST and GPx were significantly increased in patients versus patients before treatment (p < 0.001). SOD, alpha1, alpha2, beta1, beta2, gamma globulins, CRP, albumin, leukocytes and basophils were significantly decreased after treatment versus before treatment (p < 0.05). A significant correlation between CRP and UAS (r = 0.3; p = 0.011) was noted. UAS assessment revealed the efficacy of 30 d-antihistaminic treatment. Conclusions: Desloratadine exerted anti-inflammatory and antioxidant effects on CSU patients revealed by CRP. Patients’ remission was synergistic to CRP attenuation emphasizing CRP relevance for CSU clinical assessment.

Biochemical and molecular diagnosis of alpha 1 antitrypsin deficiency in a Tunisian family

Our study investigated alpha 1 antitrypsin deficiency (AATD) diagnosis in a family originated from central Tunisia and showing a familial history of asthma. Biochemical and genetic diagnosis for AATD was performed according to current diagnostic standards. AAT level quantification in affected individuals showed plasma AAT levels consistent with intermediate AATD (ranged from 0.91 to 1.04 g/L). The molecular analysis was assessed using the genotyping of the most prevalent PI*S and PI*Z SERPINA1 mutations and the sequencing of AAT coding exons for rare AATD variants detection. No PI*S or PI*Z deficient variants were seen in this family. Sequencing results showed the inheritance of the deficient rare variant PI*M(wurzburg) (P369S) at the heterozygous state in the mother and two affected siblings. However, AATD status remains unexplained in the third affected case, with no mutations detected in the AAT coding exons.