Polymorphisms of the NOS3 gene in Tunisian patients with Behçet's disease.

Behçet's disease (BD) is a multisystem inflammatory disease characterized by recurrent orogenital ulceration, ocular inflammation and skin lesions. Reduced plasma nitric oxide (NO) levels in patients with BD have been implicated in the development of the endothelial abnormalities and thrombotic complications occurring in these patients. Polymorphisms in the endothelial nitric oxide synthase gene (NOS3) have been inconsistently associated with BD. This inconsistency may derive from population stratification secondary to ethnic diversity, and consideration limited to only one rather than combinations of polymorphisms. We studied three genetic variations in the NOS3 gene: a single nucleotide polymorphism in the promoter region -786T>C, in exon 7 (Glu298Asp), and a variable number of tandem repeats in intron 4 (4a4b) of the NOS3 gene in 100 unrelated Tunisian patients with BD and 148 healthy controls. In addition, we also examined the association of NOS3 gene haplotypes with BD. Analyses of the Glu298Asp, -786T>C and 4a4b polymorphisms were made by the polymerase chain reaction (PCR) restriction fragment length polymorphism technique and PCR genotyping, respectively. The distribution of the Glu298Asp genotype differed significantly between patients with BD and controls (P = 0.01). Allele Asp298 was significantly more frequent in patients with BD than in controls (P = 0.005, OR = 1.70, 95% CI 1.14-2.54). In contrast, distribution of alleles and genotypes of -786T>C and 4a4b polymorphisms was not different between the control and BD group. However, the frequency of Asp-T-4b haplotype was significantly higher in patients with BD than in healthy controls. By gender, the signification remained only for heterozygous men (P = 0.03) and homozygous women (P = 0.02). These results suggest that Glu298Asp polymorphism of the NOS3 gene is associated with BD susceptibility in Tunisian patients.

Urinary creatine at rest and after repeated sprints in athletes: a pilot study.

Creatine plays a key role in muscle function and its evaluation is important in athletes. In this study, urinary creatine concentration was measured in order to highlight its possible significance in monitoring sprinters. The study included 51 sprinters and 25 age- and sex-matched untrained subjects as a control group. Body composition was measured and dietary intake estimated. Urine samples were collected before and after standardized physical exercise. Creatine was assessed by gas chromatography mass spectrometry. Basal urinary creatine (UC) was significantly lower in sprinters than controls (34±30 vs. 74±3 µmol/mmol creatinine, p < 0.05). UC was inversely correlated with body mass (r = -0.34, p < 0.01) and lean mass (r = -0.30, p < 0.05), and positively correlated with fat mass (r = 0.32, p < 0.05). After acute exercise, urinary creatine significantly decreased in both athletes and controls. UC is low in sprinters at rest and further decreases after exercise, most likely due to a high uptake and use of creatine by muscles, as muscle mass and physical activity are supposed to be greater in athletes than untrained subjects. Further studies are needed to test the value of urinary creatine as a non-invasive marker of physical condition and as a parameter for managing Cr supplementation in athletes.

[Molecular diagnosis of Gaucher disease in Tunisia]. / Diagnostic moléculaire de la maladie de Gaucher en Tunisie.

Gaucher disease is a lysosomal storage disorder caused by a deficiency of the enzyme acid ß-glucosidase. In order to determine the mutation spectrum in Tunisia, we performed recurrent mutation screening in 30 Tunisian patients with Gaucher disease. Screening of recurrent mutation by PCR/RFLP and direct sequencing had shown that N370S was the most frequent mutation (22/50 mutant alleles, 44%), followed by L444P mutation, which is found in 16% (8/50 mutant alleles). The recombinant allele (RecNciI) represented 14%. Our findings revealed that the genotype N370S/RecNciI was mosst frequent in patients with childhood onset and it was associated with severe visceral involvement. The screening of these three mutations provided a simple tool for molecular diagnosis of Gaucher disease in Tunisian patients and allowed also genetic counselling for their family members.

Unbalanced bone remodeling in Tunisian patients with inflammatory bowel diseases.

BACKGROUND: Bone loss is an ignored complication in inflammatory bowel diseases. Its underling mechanisms are not fully elucidated. OBJECTIVES: To investigate bone turnover in patients with inflammatory bowel diseases. METHODS: The study included 67 patients with inflammatory bowel diseases and 54 age- and sex-matched healthy subjects. Urinary degradation products of C-terminal telopeptide of type I collagen, serum osteocalcin, parathyroid hormone, 25 hydroxy vitamin D and interleukin-6 were assessed. Bone mineral density was measured by dual energy-X-ray absorptiometry and osteoporosis was defined as T score < -2.5 SD. RESULTS: Patients showed significantly higher levels of C-terminal telopeptide of type I collagen and interleukin-6 and lower levels of 25 hydroxy vitamin D. Serum osteocalcin and parathyroid hormone were in normal range. In multivariate analysis, urinary degradation products of C-terminal telopeptide of type I collagen were associated with disease activity (p=0.04) and osteocalcin was associated with parathyroid hormone (p=0.04). Urinary degradation products of Cterminal telopeptide of type I collagen and interleukin-6 were significantly increased in inflammatory bowel disease patients with osteoporosis. No association was found between osteoporosis and serum osteocalcin, parathyroid hormone and 25 hydroxy vitamin D. CONCLUSION: Bone resorption rate is increased and is associated with osteoporosis in inflammatory bowel disease patients. Inflammation, malnutrition, and hypovitaminosis D may contribute to the bone loss.

Prehypertension among adults in Great Tunis region (Tunisia): A population-based study.

PURPOSE: The present study aimed to determine the prevalence of prehypertension (preHTN) and its cardiometabolic profile in Tunisians, and to estimate the risk for coronary heart disease (CHD) according to blood pressure status. PATIENTS AND METHOD: This cross-sectional study was conducted in 2004-2005, and used a two-stage cluster sampling method to select a representative sample of the Great Tunis population. A total of 2712 individuals (1228 men and 1484 women), aged 35 to 69 years were included. Definition and classification of hypertension (HTN) was performed according to guidelines from the Joint National Committee on prevention, detection, evaluation and treatment of high blood pressure (JNC-7) report. RESULTS: The prevalence of preHTN and HTN was 56.8% and 25.0% in males, and 43.1% and 36.1% in females, respectively. Subjects with preHTN and those with HTN showed higher prevalence of diabetes, dyslipidemia, obesity and abdominal obesity than the normotensive (NT) group. The metabolic syndrome (MetS) was found in 8.0%, 17.8% and 53.8% of NT, preHT and HTN subjects, respectively. The risk of developing CHD within 10 years, as predicted by the Framingham-Anderson model, was above 15% for 3.9%, 31.1% and 65.0% among NT, preHTN and HTN subjects, respectively. In multivariate analysis, preHTN was associated with age (OR [95% CI], 1.02 [1.01-1.03]; P<0.01), male gender (2.51 [1.89-3.23]; P<0.001), obesity (2.36 [1.71-3.26]; P<0.01), abdominal obesity (1.53 [1.14-2.06]; P<0.01) and smoking (0.70 [0.53-0.92]; P<0.01). CONCLUSION: PreHTN is very common in Tunisians. It is associated with a higher prevalence of cardiometabolic risk factors and confers a higher risk for subsequent CHD. These findings support the recommendations of lifestyle modification for preHTN patients.

A novel 22bp deletion in a Tunisian phenylketonuria family.

Phenylketonuria (PKU) is an autosomal recessive metabolic disorder caused by a deficiency of phenylalanine hydroxylase. To date, more than 530 mutations in the PAH gene have been reported. In Tunisia, this disease seems to be the result of point mutations, few studies have been published about molecular defects of PKU in our country. In this study, we report a novel deletion in exon 6 of two brothers in a Tunisian family after DHPLC analysis and sequencing of the exon 6 of the PAH gene.

The G3057A LEPR polymorphism is associated with obesity in Tunisian women.

OBJECTIVES: The aim of this study was to evaluate the effect of the G3057A (rs62589000) LEPR polymorphism on obesity risk and plasma leptin, insulin, and lipid levels in a sample of the Tunisian population. DESIGN AND METHODS: Three hundred and ninety-three obese patients and 317 controls participated in this study. The G3057A genotype was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: In the entire study sample, no significant differences in genotype frequencies were observed between obese patients and controls. However, stratified analysis by gender revealed a quantitative increase in the variant allele (33.3% vs. 25.8%; χ(2)=4.90, p=0.026) in obese women (but not men) compared to controls. When a dominant model of inheritance was assumed, the GA+AA genotypes were more prevalent in these obese female patients than in controls (58.3% vs. 47.8%; χ(2)=4.08, p=0.044). Unconditional logistic regression showed that in women only, obesity risk was significantly higher for homozygotes for the variant allele (OR=2.73, 95% CI 1.03-7.21) and for carriers of GA+AA genotypes (OR=1.53, 95% CI 1.01-2.31) compared with homozygotes for the normal allele. The association between the G3057A LEPR variant and obesity remained statistically significant even after adjustment for age. No relationship was found between the G3057A LEPR polymorphism and leptin and insulin levels. Additionally, this LEPR gene variant had no effect on plasma lipid concentrations. CONCLUSION: There is evidence in this study that the G3057A LEPR polymorphism is associated with obesity in Tunisian women.

Metabolic syndrome in Tunisian psoriatic patients: prevalence and determinants.

BACKGROUND: A significant association between psoriasis and the metabolic syndrome (MetS) has been frequently reported. OBJECTIVE: The aim of this study was to specify the main factors that determine the MetS in psoriatic Tunisian patients. METHODS: A case-control study has included 164 psoriatic patients and 216 controls. RESULTS: The prevalence of MetS was higher in cases than in controls but without statistical differences [35.5% vs. 30.8%, odds ratio (OR): 1.39 CI: 0.88-2.18; P=0.095]. According to gender, the prevalence of MetS was significantly increased only in psoriatic women (47.4% vs. 30%, OR: 1.89, CI: 1.11-3.21; P=0.01). A multiple logistic regression, considering the effect of age, and gender, showed that the prevalence of MetS was significantly higher in cases than in controls (OR: 1.73, CI: 1.06-2.82; P=0.03). MetS components analysed seperately showed a significantly higher prevalence of decreased high-density lipoprotein cholesterol (HDLc) (60.9% vs. 35.9%, OR: 2.77, CI: 1.8-4.27, P<0.001) and for increased hypertension (50% vs. 40%, OR: 1.48, CI: 0.97-2.257, P=0.04) in psoriatic patients. According to gender, HDLc was significantly decreased in both genders (male: OR: 2.075, CI: 1.24-3.47, P=0.004; female: OR: 3.58, CI: 2.07-6.19, P<0.0001), while hypertension was increased only in psoriatic men (OR: 2.09, CI: 1.24-3.51, P=0.004) and abdominal obesity only in psoriatic women (OR: 2.31, CI: 1.30-4.11, P=0.002). CONCLUSION: Decreased HDLc is the main biological abnormality that characterized MetS in Tunisian psoriatic patients. Moreover, contrary to men, psoriatic women have shown a significantly higher prevalence of MetS, which is, in addition to decreased HDLc, mainly attributed to abdominal obesity.

Metabolic syndrome is associated with gastroesophageal reflux disease based on a 24-hour ambulatory pH monitoring.

Several studies have focused on the relationship between metabolic syndrome and gastroesophageal reflux disease (GERD). They were based on GERD complications, whereas little is known about the association between metabolic syndrome and objectively measured esophageal acid exposure. The aim of our study was to assess the relationship between metabolic syndrome and GERD based on a 24-hour pH testing. It was a cross-sectional study including 100 consecutive patients who underwent a 24-hour pH-metry monitoring and were assessed for the five metabolic syndrome components as well as for body mass index (BMI). Among the 100 patients, 54 had a pathological acid GERD. The 46 GERD-free patients represented control group. Sex distribution was comparable between both groups but GERD patients were older than controls (44.59 vs. 37.63 years, P= 0.006) and more often obese or with overweight (83.3 vs. 60.9%, P= 0.01). Frequency of metabolic syndrome as a whole entity was higher among patients with GERD than those without GERD (50 vs. 19.56%; P= 0.002) with a crude odds ratio of 4.11 (95% confidence interval: 1.66-10.14). Multivariate regression analysis showed that metabolic syndrome as well as an age ≥ 30 years were independent factors associated to GERD but not BMI and sex. Abnormal waist circumference and fasting glucose level ≥ 100 mg/L were the only independent factors among the five components of metabolic syndrome. Metabolic syndrome but not BMI was an independent factor associated to GERD. These results confirm the hypothesis that central obesity is associated to GERD.

Homogénéité mutationnelle de la glycogénose de type Ia en Tunisie.

The glycogen storage disease type Ia (GSD Ia) is a rare inherited disorder, with autosomal recessive determinism. It is characterized by hepatomegaly, short stature and hypoglycemia with lactic acidemia. The confirmation of diagnosis is based on the enzymatic assay performed on liver biopsy. For Tunisians patients, this biochemical test is performed abroad. The aim of our study is the molecular characterization of GSD Ia in Tunisian patients and the development of a molecular diagnosis tool. Our study included 27 patients from 23 unrelated families, mutation analysis revealed that the R83C mutation is the most frequent (65%, 30/46 mutant alleles), followed by the R170Q mutation (30%, 14/46 mutant alleles). The homogeneity of mutation spectrum of GSD Ia in Tunisia allows the development of a cost effective and reliable tool for the confirmation of clinical diagnosis among suspected GSD Ia patients.

Ketosis-onset diabetes in Tunisian adults: immunological markers and beta-cell function.

The aim of this study in Tunisia was to classify ketosis-onset diabetes in adult patients. All patients aged > 30 years without known diabetes, presenting with ketosis and admitted to our department were studied. Patients with secondary or gestational diabetes and those on corticoid therapy or with coinciding infection were excluded. The data included clinical characteristics, immunological markers and beta-cell function. Of the 63 patients, islet-cell antibodies were present in 27.0%, glutamic acid decarboxylase antibodies in 25.4% and thyrosin phosphatase antibodies in 19.0%. Beta-cell functional reserve was preserved in 54.0%. Our results confirm that patients with ketosis-onset diabetes mellitus in adulthood are a heterogeneous group.

[Late revelation of homocysteinuria: clinical, biological and progressive aspects]. / Homocystéinurie à révélation tardive : aspect clinique, biologique et évolutif.

UNLABELLED: Homocysteinuria is a metabolic disorder with defect in genes encoding for methionine metabolism enzymes. The clinical features consist in: ophthalmic, neurological, orthopedic and vascular manifestations. It is generally diagnosed in childhood. Vascular involvements characterize adult's forms. We report one case. OBSERVATION: A 26-year-old man, who has lentis ectopia and a recent epilepsy, was hospitalized for deep vein thrombosis. Regarding the marfanoid phenotype and the high level homocysteinemia (231 micromol/L), homocysteinuria was suspected. Amino acid chromatography and reduced CBS activity were used to confirm the diagnosis. Vitamin enriched diet with vitamin B6 and folates has reduced slightly the homocysteine level. CONCLUSION: Homocysteinuria must be diagnosed early since a simple vitamin supply could ameliorate prognosis and decrease complications.

[Prevalence of conventional cardiovascular risk factors in the Great Tunis population]. / Prévalence des facteurs de risque cardiovasculaires conventionnels dans la population du Grand Tunis.

BACKGROUND: This study was designed to determine the prevalence of main cardiovascular risk factors in the population of Great Tunis. SUBJECTS AND METHODS: This cross-sectional study included 2483 individuals aged 35 to 70 years dwelling in the Great Tunis region, recruited between March 2004 and June 2005. The sample was weighted using the inverse of response rate according to governorate, district and sex. RESULTS: Obesity and abdominal obesity were observed respectively in 34 and 48% of subjects. The prevalence of these two factors was particularly elevated in females (46 and 69% respectively). Hypertension was common (31%), especially in women (36%). Diabetes mellitus and dyslipemia were found in 15 and 21% of subjects, respectively, without difference according to sex. More than half of men and 8% of women were current smokers. CONCLUSION: The prevalence of conventional cardiovascular risk factors is dramatically high in the population of Great Tunis. These findings predict a future expansion of cardiovascular diseases in this population. Profound changes of lifestyle and dietary habits of Tunisians are needed to reduce the risk of cardiovascular morbidity and mortality.

[An overview of neurometabolic diseases in Tunisia. a 3-year prospective study]. / Diagnostic et prise en charge des maladies neurométaboliques en Tunisie. Etude prospective sur trois ans.

INTRODUCTION: Neurometabolic diseases are a large group of genetic diseases. In our country, the diagnostic and therapeutic approach to theses diseases is rather difficult. The aim of our study was to determine the frequency of neurometabolic diseases in the hospital population, to describe the problems in diagnosing these conditions and difficulties encountered during patient care. Our goal was to propose guidelines for a practical diagnostic and therapeutic approach to neurometabolic disorders in our country. METHODS: We have conducted a prospective study over a 3-year period including all patients diagnosed with "metabolic disease" and followed at the Child and Adolescent Neurology Department of the National Institute of Neurology of Tunis. RESULTS: One hundred and thirty-six patients were included (2.4% of our patients). Mean age was 7.3 +/- 5.1 years. Mean age at onset was 4.3 years. There was a high consanguinity rate. Respiratory chain defects were the most frequently suspected diseases (16.9%), followed by lysosomal diseases (8.8%). Chromatography, initially systematically prescribed, became targeted with a higher diagnostic efficacy. Metabolic diseases diagnosed as certain, represented 22% of the studied cases. This can be explained by the insufficiency of available laboratory tests of confirmation. The prescription of specific treatment was insufficient, even for confirmed pathologies (14.7%) because of the high cost of these therapies. CONCLUSION: The diagnostic approach has to be rational, targeted, multidisciplinar and conducted within a care network. Diagnostic priority should focus on treatable neurometabolic diseases. The establishment of a systematized registry and neonatal screening for the main treatable neurometabolic diseases constitute the final objective of our work to prepare for biochemical and genetic studies.

Phenotypic spectrum of fucosidosis in Tunisia.

Fucosidosis (OMIM 230000) is a rare autosomal recessive lysosomal disorder due to deficient α-L-fucosidase activity(EC 3.2.1.51), leading to the accumulation of fucose-containing glycolipids and glycoproteins in various tissues. This study contained the largest ever Tunisian survey of fucosidosis patients, diagnosed during the period 1987-2007. The clinical pictures and outcomes of these patients are compared with literature data. Ten patients (8 boys and 2 girls) from six unrelated families were diagnosed at a mean age of 29 ± 10.3 months. Six of the patients were diagnosed as having the more severe phenotype. The other four cases presented the low progressive phenotype. This distinction was determined by the presence or absence of angiokeratoma and age of death. For all of the patients in our survey, early motor development was more severely delayed than described in the literature. Six patients presented psychomotor decline during the second year of life. Clinical features consist of variable mental retardation (all patients), progressive spastic quadriplegia (6/10 cases), coarse facies (9/10 cases), growth retardation (7/9 cases), visceromegaly (3 cases), angiokeratoma corporis diffusum (4 cases), recurrent bronchopneumonias (all cases), seizures (4 cases) and variable degrees of dysostosis multiplex (all cases). Portal cavernoma, never described in the literature, was observed in one patient. The outcomes were severe in this survey, probably owing to restricted health care; death occurred in 6 of the 10 patients before age 10 years, following recurrent pulmonary infections and neurological deterioration. No intrafamilial variability was noted in the multiplex families. The clinical presentation and outcomes of some of these patients were consistent with the continuous clinical spectrum of severity in fucosidosis attested by most clinical studies.

The -2548G/A LEP polymorphism is associated with blood pressure in Tunisian obese patients.

OBJECTIVE: To examine the association of a common -2548G/A (rs7799039) promoter variant of the human leptin gene (LEP) with obesity or body mass index (BMI) and its associated phenotypes such as blood pressure variability and the prevalence of hypertension in a sample of the Tunisian population. DESIGN AND METHODS: Two hundred and twenty-nine obese patients were screened and compared with 251 normal weight subjects. The -2548G/A LEP polymorphism was analysed by PCR-RFLP procedure. RESULTS: No significant association was found between the -2548G/A polymorphism and obesity or BMI. However, in obese patients subjects with AA genotype had significantly higher systolic (p = 0.003) and diastolic (p = 0.002) blood pressure compared with those with GA or GG genotypes. Stratified analysis by gender revealed that male patients but not female homozygous for -2548A allele exhibited significantly increased systolic (p = 0.01) and diastolic (p<0.001) blood pressure than did carriers of -2548G allele. Multiple linear regression analysis revealed that AA genotype significantly affect systolic and diastolic blood pressure in obese men. Additionally, significant association between AA genotype and higher prevalence of hypertension was found in male patients (p = 0.03). CONCLUSION: The present study showed that the -2548G/A LEP polymorphism is associated with blood pressure in obese male patients.

Osteoma of the calvaria in L-2-hydroxyglutaric aciduria.

L-2-Hydroxyglutaric aciduria (L-2-OHGA) is a rare autosomal recessive neurometabolic disease linked to chromosome 14q21.1 and is caused by mutations in the gene that most likely encodes L: -2-hydroxyglutarate dehydrogenase, which normally catalyses L: -2-hydroxyglutarate to alpha-ketoglutarate. It is characterized by progressive mental deterioration, pyramidal and cerebellar syndromes, macrocephaly and marked polycystic white-matter degeneration mainly involving frontal lobes. Brain tumours of variable nature have frequently been observed in L-2-OHGA. We report a patient affected by this disease who at the age of 20 years developed a bone tumour involving the right frontal region of the calvaria. He had first presented at the age of 10 years with psychomotor delay, clumsy gait and moderate mental impairment. Examination showed macrocephaly, cerebellar ataxia and quadripyramidal syndrome. Brain MRI showed low signal intensities on T1-weighted images and high signal intensities on T2-weighted images in cerebral subcortical white matter. Serum and urinary amino acid assay was normal. Urinary 2-hydroxyglutaric acid was 1418 mmol/mol creatinine (controls <25). Analysis of the L-2-hydroxyglutarate dehydrogenase gene revealed a homozygous mutation in exon 2 (A320G). At the age of 20 years, an osteoma of the right frontal bone was diagnosed. This finding reinforces the opinion concerning the association of L-2-OHGA and tumorigenesis and prompted us to verify the possible responsibility of some overproduced substances in this disease for the development of tumours and to look for any correlation between the type of mutation in the L-2-OHGA gene and the tumorigenic potential observed in some patients affected by this disease.

Mutation spectrum of glycogen storage disease type Ia in Tunisia: implication for molecular diagnosis.

Glycogen storage disease type Ia (GSD Ia; OMIM 232200) is an autosomal recessive disorder of glycogen metabolism caused by a deficiency of the microsomal glucose-6-phosphatase (G6Pase). It is characterized by short stature, hepatomegaly, hypoglycaemia, hyperuricaemia, and lactic acidaemia. Various mutations have been reported in the G6Pase gene (G6PC). In order to determine the mutation spectrum in Tunisia, we performed mutation analysis in 22 Tunisian type I glycogen storage disease (GSD I) patients belonging to 18 unrelated families. All patients were clinically classified as GSD Ia. The R83C mutation was found to be the major cause of GSD Ia, accounting for 24 of 36 mutant alleles (66.6%), The R170Q mutation was the second most frequent mutation; it accounts for 10 of 36 mutant alleles (27.7%). The R83C and R170Q mutations could be rapidly detected by PCR/RFLP. Since the majority of Tunisian patients carried R83C and/or R170Q mutations, we propose direct screening of these mutations as a rapid, valuable and noninvasive tool for diagnosis of GSD Ia in Tunisian as well as in Northern African populations.

Apolipoprotein B signal peptide polymorphism: distribution and influence on lipid parameters in Tunisian population.

Apolipoprotein B (apo B) is the major protein component of LDL, VLDL and chylomicrons. Numerous polymorphisms of the apolipoprotein B gene have been described. Particularly, the insertion/deletion polymorphism located in the coding part of the signal peptide of apo B, associated with modification of lipid concentrations and the risk of cardiovascular disease, has been reported in the general population. No such study in the Tunisian population has been performed. The aim of our study was to assess the effect of insertion/deletion polymorphism of the apolipoprotein B gene on lipid levels in a sample of the Tunisian population. A total of 458 unrelated subjects (321 men and 137 women) were included. The insertion/deletion polymorphism was determined by electrophoresis on polyacrylamide gels after PCR amplification. The relative frequencies of the Ins and Del alleles were 0.74 and 0.26, respectively. These frequencies were similar to those found in other Caucasian populations. There was no significant difference in serum TC, TG, and HDL-C levels due to the influence of the genotypes. However, significant variation among the three genotypes was seen for LDL-cholesterol (p<0.001) and apo B (p<0.001) levels. Individuals homozygous for the Del allele had higher levels than individuals homozygous for the Ins allele, while individuals heterozygous for both alleles exhibited intermediate levels. When the data were analyzed in men and women separately, a similar effect was seen in both groups. Our results show that distribution of apo B insertion/deletion polymorphism in Tunisians is similar to other Caucasian population and confirm the reported association with serum LDL-cholesterol and apo B concentrations.

[XbaI polymorphism of apolipoprotein B gene in a Tunisian population: alleles frequencies and relationship with plasma lipid parameters]. / Polymorphisme XbaI du gène de l'apolipoprotéine B dans une population tunisienne: fréquences alléliques et relation avec les paramètres lipidiques plasmatiques.

Apolipoprotein B (Apo B) is a component of chylomicrons, low-density lipoproteins (LDL), very low density lipoproteins (VLDL), and intermediate-density lipoproteins (IDL) and is the ligand for the LDL receptor. Thereby, Apo B plays a central role in lipoprotein metabolism and in maintaining the normal homeostasis of serum cholesterol levels. Several Apo B restriction fragment length polymorphisms (XbaI, EcoRI, MspI) have been reported to be associated with variation in lipid levels, obesity and/or coronary artery disease. To date, no data are available on relationship between XbaI Apo B polymorphism and lipid levels in Tunisian population. Here, we report frequencies of the XbaI polymorphism of the Apo B gene and we assess the effect of this polymorphism on lipid and lipoprotein concentrations in Tunisian population. Blood samples from 296 Tunisian individuals (112 women and 184 men, aged 51.4+/-9.6 years), were analysed for total cholesterol, triglycerides, HDL-cholesterol and apolipoproteins A1 and B. In parallel, genotyping by means of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) was performed. The XbaI polymorphism was associated with differences in plasma cholesterol (p=0.04), triglyceride (p=0.02) and apolipoprotein A1 (p=0.004), individuals with the genotype X1X1 have the lowest mean levels and those with the genotype X2X2 have the highest, with the individuals heterozygous for the polymorphism having intermediate levels. According to sex, the XbaI polymorphism effect was only observed for triglyceride in men. Thus, the results demonstrate an influence of XbaI polymorphism of Apo B gene on serum total-cholesterol, triglycerides and apolipoprotein A1 concentrations among Tunisian population.