The mutational spectrum of hunter syndrome reveals correlation between biochemical and clinical profiles in Tunisian patients.

BACKGROUND: Mucopolysaccharidosis type II (MPS II) or Hunter syndrome is an X-linked recessive lysosomal storage disorder resulting from deficient activity of iduronate 2-sulfatase (IDS) and the progressive lysosomal accumulation of sulfated glycosaminoglycans (GAGs). METHODS: A diagnosis of MPS II or Hunter syndrome was performed based on the following approach after a clinical and paraclinical suspicion. Two biochemical and molecular tests were carried out separately and according to the availability of the biological material. RESULTS: All patients in this cohort presented the most common MPS II clinical features. Electrophoresis of GAGs on a cellulose acetate plate in the presence of a high concentration of heparane sulfate showed an abnormal dermatan sulfate band in the patients compared with that in a control case. Furthermore, leukocyte IDS activity ranged from 0.00 to 0.75 nmol/h/mg of leukocyte protein in patients. Five previously reported mutations were identified in this study patients: one splice site mutation, c.240 + 1G > A; two missense mutations, p.R88P and p.G94D; a large deletion of exon 1 to exon 7; and one nonsense mutation, p.Q396*. In addition, two novel alterations were identified in the MPS II patients: one frame shift mutation, p.D450Nfs*95 and one nonsense mutation, p.Q204*. Additionally, five known IDS polymorphisms were identified in the patients: c.419-16 delT, c.641C > T (p.T214M), c.438 C > T (p.T146T), c.709-87G > A, and c.1006 + 38 T > C. CONCLUSIONS: The high level of urine GAGs and the deficiency of iduronate 2-sulfatase activity was associated with the phenotype expression of Hunter syndrome. Molecular testing was useful for the patients' phenotypic classification and the detection of carriers.

CRP relevance in clinical assessment of chronic spontaneous urticaria Tunisian patients.

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.

Factor H and CFHR1 polymorphisms associated with atypical Haemolytic Uraemic Syndrome (aHUS) are differently expressed in Tunisian and in Caucasian populations.

Several polymorphisms in the complement components factor H and CFHR1 are associated with higher risk to develop atypical Haemolytic Uraemic Syndrome (aHUS) in Caucasians. We have determined the prevalence of these polymorphisms in Tunisian controls by using genetic and immunological techniques. No differences in the frequency of the factor H risk alleles c.-331C>T, c.2089A>G or c.2881G>T between Tunisian and Caucasians were found. On the contrary, the analysis of CFHR1 polymorphism revealed a higher frequency of Tunisian individuals homozygous for the CFHR1*Del (deleted) allele, and of individuals presenting the CFHR1*A phenotype. These results suggest distinct contributions of factor H and CFHR1 polymorphisms to aHUS in Tunisian and Caucasian populations.

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.

[Alpha 1 antitrypsin polymorphism associated to asthma and emphysema in a central Tunisian population]. / Polymorphisme de l'alpha 1 antitrypsine associé à l'asthme et l'emphysème pulmonaire dans une population du centre tunisien.

INTRODUCTION: more than 100 alleles have been described on the alpha 1 antitrypsin gene. Normal variants (PiM1, PiM2 and PiM3) encodes AAT molecules which are different but functional and normally secreted. The more frequent risk variants are PiS and PiZ. In this study, an AAT polymorphism analysis in correlation with pulmonary diseases was conducted. MATERIAL AND METHODS: analyses were performed on 96 asthmatics, 67 emphysema cases and 318 control subjects. Alpha 1 antitrypsin phenotypes were studied by quantitative determination of AAT concentration and isoelectrofocusing. Genotyping was performed by RFLP PCR. RESULTS: PiM1, PiM2, PiM3, PiS and PiZ allelic frequencies were calculated (0.7395, 0.2291, 0.0156, 0.0104, 0.0052 in asthmatics; 0.7547, 0.1716, 0.0298, 0.0298, 0.0149 in emphysema patients and 0.8030, 0.1525, 0.0408, 0.006, 0.0000 in controls, respectively). Results showed an increase in PiM2 allele frequencies in both patients' groups compared to controls. Allelic frequencies difference is significant only with the asthmatic group (p=0,0179). PiS and PiZ deficiency alleles are more prevalent in the emphysema (0.0298, 0.0149) than in the asthmatic subjects (0.0104, 0.0052). Meanwhile, no significant difference in PiS and PiZ allelic frequencies was observed between patients and controls. CONCLUSION: PiM2 allele can be considered as genetic risk factor for asthma. PiS and PiZ alleles are very rare in Tunisia in comparison with the European population, leading to a very small contribution in pulmonary diseases pathogenesis in Tunisia.

[Oxidant stress and cardiovascular absolute risk in Tunisian type 2 diabetes]. / Stress oxydant et risque cardiovasculaire absolu chez des diabétiques de type 2 du centre tunisien.

INTRODUCTION: cardiovascular diseases constitute the most hefty complications in diabetes. Absolute cardiovascular risk (ACVR) can be estimated by many equations that are continuously criticised. The aim is, in one hand, to evaluate ACVR in type 2 diabetes and, in the other hand, is to establish correlations between ACVR and oxidant-antioxidant status. MATERIAL AND METHODS: 183 type 2 diabetes and 200 controls were admitted. ACVR assessment was calculated following Laurier equation. Oxidant status was evaluated by the measure of homocysteine, hydrogen peroxide (H2O2) and LDL thiobarbituric reactive oxygen substances (LDL-TBARS). Antioxidant status was evaluated by the measure of superoxide dismutase (SOD) activity, glutathione peroxidase (GPx), total antioxidant status (TAS) vitamins A, E and zinc. Glycated haemoglobin (HbA1c) and microalbuminuria were assessed by turbidimetry. RESULTS: ninety percent of diabetes belonged to moderate and high ACVR groups. In diabetic men ACVR was doubled each elevation of 4 micromol/L homocysteine, of 50 micromol/L of H2O2 and of 20 mg/L of microalbuminuria. High risk ACVR group showed the lowest SOD activity, zincemia and the highest HbA1c. No significant difference was found in LDL-TBARS, TAS, GPx, vitamins A, E between the different ACVR groups. The strong relation between homocysteine and ACVR confirms homocysteine atherosclerotic role. Homocysteine auto-oxidation produces H2O2 leading to LDL-TBARS increase. Microalbuminuria-ACVR association verifies its vasculopathy predictor role. Urinary albumin leakage may be consequent to the hyperhomocysteinemia found in diabetes. CONCLUSION: homocysteine introduction in ACVR assessment equation may ameliorate this estimation.

Alpha 1 antitrypsin polymorphism in the Tunisian population with special reference to pulmonary disease.

OBJECTIVES: The study investigated alpha 1 antitrypsin (AAT) gene polymorphism in the Tunisian population. We aimed to analyze the correlation between Pi polymorphism and the risk of developing chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: We focused our study on two samples originating from the Tunisian centre: 318 healthy controls and 90 patients suffering from COPD. Data analysis was investigated by AAT level quantification, serum isoelectric focusing (IEF) and RFLP-PCR performed with PiS and PiZ allele specific primers. RESULTS: We calculated PiM1, PiM2, PiM3, PiS and PiZ allele frequencies in patients and controls. The difference in allele frequencies is significant only for the PiM2 allele (P=0.00378). In COPD patients, we note the presence of PiZ allele. This allele mainly observed in European populations, is rare in sub-Saharian populations and not described in North Africa. CONCLUSION: PiZ allele is found in COPD sample and never in Tunisian controls. However, no significant difference in PiZ allele frequency between patients and controls can be concluded. PiM2 allele, which is considered as "normal" variant can be associated with COPD risk.

[C3 complement polymorphism in patients suffering from obstructive chronic bronchopneumopathy in Tunisia]. / Polymorphisme du C3 du complément chez des patients atteints de bronchopneumopathie chronique obstructive en Tunisie.

We analysed the C3*S and C3*F polymorphism of the third component of the complement (C3), first at the protein level by the electrophoresis of the plasma on agarose gel and second on the gene level by the ARMS PCR technique. We determined the phenotypic and genotypic frequencies of the C3 on a sample of 90 patients suffering from the obstructive chronic bronchopneumopathy (OCBP) disease. Comparisons have been done with frequencies observed on a control sample of 437 healthy individuals from the Tunisian population in order to establish a putative correlation between the polymorphism studied and the disease. Frequencies of the C3*S and C3*F alleles in OCBP patients are 0,788 and 0,212 respectively. They are not significantly different from those observed in control sample (0,834 and 0,152 respectively). Therefore, no correlation is observed between the C3 polymorphism and the risk of developing the OCBP disease.