Leptin and Leptin receptor polymorphisms, plasma Leptin levels and obesity in Tunisian volunteers.

Adipose tissue is an important endocrine organ that secretes a number of adipokines, like Leptin (LEP). The aim this study was to investigate the prevalence of single nucleotide polymorphisms in LEP gene (LEP 3'UTR A/C, -2548 G/A) and LEPR (K109R and Q223R) and their association with Leptin level and obesity. We recruited 169 non-obese (body mass index [BMI] = 24.51-3.69 kg/m2 ) and 160 obese (BMI = 36-4.78 kg/m2 ) patients. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism, BMI was calculated, and Leptin level was measured by ELISA. Statistical analyses were performed by spss19.0. According to LEP 3'UTR A/C polymorphism, AC and CC genotype carriers had higher Leptin levels than AA genotype carriers, respectively, 31[0.05-148.8] (P = .008) vs 41[0.05-111.6] (P = .003). The K109R polymorphism was associated with obesity (P = .025) and seems to significantly decrease the LEP levels (P < .001). Concerning LEP G2548A polymorphism, our results showed that the OR of obesity associated with 2548 AA/GG was 1.87[1.106-2.78] P = .028 vs 1.41[1.035-1.85] P = .045 for 223AA/GG polymorphism. In our haplotype analysis, one haplotype seems to be the more protective and one other seems to be the highest risk to obesity. LEP 3'UTR A/C and LEPR K109R polymorphisms were associated with Leptin level and obesity.

[Is paraoxonase 1 a marker of cardiovascular risk in youth with type 1 diabetes? (Study about 109 cases)]. / La paraoxonase 1: un marqueur de risque cardiovasculaire chez les jeunes diabétiques de type 1 ? (109 cas).

OBJECTIVES: We purpose to verify if paraoxonase 1 (PON1) activity may be a marker of cardiovascular risk in a young Tunisian population with type 1 diabetes (T1D). METHODS: PON1 activity was measured by a kinetic method using paraoxon as substrate. The other parameters were determined by automated methods. RESULTS: One hundred and nine children and adolescents with T1D and 97 healthy subjects were involved in this study. PON1 activity and PON1/HDL-cholesterol ratio were significantly decreased in diabetics (303 ± 174 vs. 372 ± 180 U/L and 221 ± 139 vs. 298 ± 20 1U/mmol, P=0.006, P=0.002, respectively) compared to controls. A significant increase in total cholesterol, LDL-c and microalbuminuria was observed in diabetics compared to controls. PON1 activity was decreased by 9.5% in patients with diabetes duration ≥ 6 years, by 28.4% for those with fasting glycemia ≥ 7 mmol/L (P<0.001), by 14% in those with HbA1c ≥ 8% and by 12.3% for diabetics with dyslipidemia. PON1 activity is reduced when the number of cardiovascular risk factors increases (P<0.001). CONCLUSION: PON1 seems to be associated to cardiovascular risk markers in T1D. This result remains to be seen. Nevertheless, improving PON1 activity could be a significant target for reducing cardiovascular risk.

Combined effects of the C161T and Pro12Ala PPARγ2 gene variants with insulin resistance on metabolic syndrome: a case-control study of a central Tunisian population.

We investigated the synergism between variants at the PPARγ locus (C161T and Pro12Ala polymorphisms) with insulin resistance on metabolic syndrome (MS). Five hundred twenty-two subjects were investigated for biochemical and anthropometric measurements. The diagnosis of MS was based on the IDF definition (2009). The HOMA 2 was used to determine HOMA-ß, HOMA-S, and HOMA-IR from FPG and FPI concentrations. PCR-RFLP was performed for DNA genotyping. We showed that carriers of the Pro/Pro had a significantly higher FPG, FPI, and HOMA-IR. In addition, Pro/Pro subjects also display reduced HOMA-ß and HOMA-S together compared to X/Ala (Pro/Ala and Ala/Ala) subjects. Furthermore, subjects with C/C have a significantly lower FPG, FPI, and HOMA-IR and higher HOMA-S compared to X/T (C/T and T/T) subjects. The C/C genotype carriers with an Ala allele group had significantly reduced FPG, FPI, HOMA-IR, and TG and elevated HOMA-S and HOMA-ß than the different genotype combinations. We suggest that the haplotype composed of the C/C genotype carriers with an Ala allele of PPARγ2 group enhances susceptibility to the MS in a central Tunisian population.

Interaction Effects of the Leu162Val PPAR α and Pro12Ala PPAR γ 2 Gene Variants with Renal Function in Metabolic Syndrome Population.

Leu162Val PPAR α and Pro12Ala PPAR γ 2 were investigated for their individual and their interactive impact on MS and renal functionality (RF). 522 subjects were investigated for biochemical and anthropometric measurements. The diagnosis of MS was based on the IDF definition (2009). The HOMA 2 was used to determine HOMA- ß , HOMA-S and HOMA-IR from FPG and FPI concentrations. RF was assessed by estimating the GFR. PCR-RFLP was performed for DNA genotyping. Allele frequencies were 0.845 for Pro and 0.155 for Ala, and were 0.915 for Leu and 0.085 for Val. We showed that carriers of the PPAR α Val 162 allele had lower urea, UA and higher GFR compared to those homozygous for the Leu162 allele. Subjects carried by PPAR γ 2Ala allele had similar results. They also had reduced FPG, FPI and HOMA-IR, and elevated HOMA- ß and HOMA-S compared to those homozygous for the Pro allele. Subjects were divided into 4 groups according to the combinations of genetic alleles of the 2 polymorphisms. Subjects carrying the Leu/Val with an Ala allele had lower FPG, PPI, HOMA-IR, urea, UA levels, higher HOMA- ß , HOMA-S and GFR than different genotype combinations. Leu162Val PPAR α and Pro12Ala PPAR γ 2 can interact with each other to modulate glucose and insulin homeostasis and expand their association with overall better RF.

Molecular characterization of Tunisian families with abetalipoproteinemia and identification of a novel mutation in MTTP gene.

BACKGROUND: Abetalipoproteinemia (ABL; OMIM 200100) is a rare monogenic disorder of lipid metabolism characterized by reduced plasma levels of total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) and almost complete absence of apolipoprotein B (apoB). ABL results from genetic deficiency in microsomal triglyceride transfer protein (MTP; OMIM 157147). In the present study we investigated two unrelated Tunisian patients, born from consanguineous marriages, with severe deficiency of plasma low-density lipoprotein (LDL) and apo B. METHODS: Intestinal biopsies were performed and The MTTP gene was amplified by Polymerase chain reaction then directly sequenced in patients presenting chronic diarrhea and retarded growth. RESULTS: First proband was homozygous for a novel nucleotide deletion (c. 2611delC) involving the exon 18 of MTTP gene predicted to cause a non functional protein of 898 amino acids (p.H871I fsX29). Second proband was homozygous for a nonsense mutation in exon 8 (c.923 G > A) predicted to cause a truncated protein of 307 amino acids (p.W308X), previously reported in ABL patients. CONCLUSIONS: We discovered a novel mutation in MTTP gene and we confirmed the diagnosis of abetalipoproteinemia in new Tunisian families. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8134027928652779.

Grip strength is a predictor of bone mineral density among adolescent combat sport athletes.

The aim of this study was firstly to investigate the correlation between bone parameters and grip strength (GS) in hands, explosive legs power (ELP), and hormonal parameters; second, to identify the most determinant variables of bone mineral density (BMD) among adolescent combat sport athletes. Fifty combat sport athletes aged 17.1 ± 0.2 year were compared with 30 sedentary subjects matched for age, height, and pubertal stage. For all subjects, the BMD in deferent sites associated with anthropometric parameters were measured by dual-energy X-ray absorptiometry. The growth hormone (GH) and testosterone (TESTO) concentrations were tested. The GS in dominant (GSDA) and nondominant arms (GSNDA) and ELP were evaluated. All BMD measured were greater in athletes than in sedentary group (p<0.01). The GS and ELP showed higher values in athletes than in sedentary group (p<0.01). The BMD in all sites were correlated with weight, but without correlation with height. The GSNDA and ELP were significantly correlated with BMD of both spine and legs. The GH was correlated with the BMD of whole body and spine (p<0.05). The TESTO was only correlated with BMD of the arms (p<0.01). The best predictor of BMD measurements is GSNDA. This study has proved the osteogenic effect of combat sports practice, especially judo and karate kyokushinkai. Therefore, children and adolescent should be encouraged to participate in combat sport. Moreover, it suggested that the best model predicting BMD in different sites among adolescent combat sports athletes was the GSNDA.

[Butyrylcholinesterase activity in schizophrenic patients]. / Étude de l'activité butyrylcholinestérase chez des patients schizophrènes.

Butyrylcholinesterase (BChE) is an enzyme that has been investigated for its putative role in neurodegenerative and neuropsychiatric disorders. The aim of our work was to study BChE activity variations in schizophrenic patients and to investigate the involvement of this enzyme in schizophrenia and the importance of determining its activity in this disease. This cross-sectional study was carried out 131 (104 males and 27 females, mean age  = 38.0  ±â€Š 11.4 years) patients with chronic schizophrenia according DSM-IV criteria and 90 (64 males and 26 females, mean age  = 37.1  ±  15.9 years) healthy controls. Plasma BChE activity was determined by a kinetic method on Integra 400plus(TM) (Roche Diagnostics). Patients with schizophrenia had higher plasma BChE activity than controls (P < 0.0001). Female patients had higher BChE activity and smokers had lower BChE activity than non-smokers either in patients and controls. In patients with schizophrenia, BChE activity was not differed with age, alcohol status and clinical sub-types, and was not correlated to duration of illness. Concerning therapeutic features, BChE activity was higher in patients treated with antipsychotics monotherapy than those treated with an association of antipsychotic and anticholinergic drugs, without significant difference (P  = 0.196). Schizophrenic patients showed an increase BChE activity, which could be related to the pathophysiology of schizophrenia.

[Inherited tubular renal acidosis]. / Acidose tubulaire rénale héréditaire.

Renal tubular acidosis (RTA) is a tubulopathy characterized by metabolic acidosis with normal anion gap secondary to abnormalities of renal acidification. RTA can be classified into four main subtypes: distal RTA, proximal RTA, combined proximal and distal RTA, and hyperkalemic RTA. Distal RTA (type 1) is caused by the defect of H(+) secretion in the distal tubules and is characterized by the inability to acidify the urine below pH 5.5 during systemic acidemia. Proximal RTA (type 2) is caused by an impairment of bicarbonate reabsorption in the proximal tubules and characterized by a decreased renal bicarbonate threshold. Combined proximal and distal RTA (type 3) secondary to a reduction in tubular reclamation of bicarbonate and an inability to acidify the urine in the face of severe acidemia. Hyperkalemic RTA (type 4) may occur as a result of aldosterone deficiency or tubular insensitivity to aldosterone. Clinicians should be alert to the presence of RTA in patients with an unexplained normal anion gap acidosis, hypokalemia, recurrent nephrolithiasis and nephrocalcinosis. The mainstay of treatment of RTA remains alkali replacement.

Influence of hypercalcic and/or hyperoxalic diet on calcium oxalate renal stone formation in rats.

OBJECTIVE: To test whether increasing dietary calcium intake prevents calcium oxalate stone formation when the diet is oxalate-rich. Material and methods. Four groups, eight rats in each, were subjected to a lithogenic diet by the addition of 0.5% ethylene glycol to drinking water for 3 weeks. The first group, used as a control, simultaneously received a standard diet. The second group was supplemented with calcium at 500 mg/100 g of diet and the third group with oxalate at 3 g/100 g of diet. The diet given to the last group was supplemented with similar doses of calcium and oxalate. One day before the end of treatment, each animal was placed in a metabolic cage to collect 24-h urine samples and determine urinary parameters. The kidneys were removed to determine calcium oxalate deposits and for histological examination. RESULTS: The number of calcium oxalate crystals in renal tissue was highest in the oxalate group and calcium oxalate deposits were also found to be elevated in this group. Hyperoxaluria and hypocitraturia, induced by a oxalate-rich diet, seemed to be the major causes contributing to aggravated renal stone formation. The protective effect of dietary calcium supplementation, which was clear in the calcium + oxalate group, was probably due to intestinal binding of oxalate by calcium, thereby reducing urinary oxalate excretion. CONCLUSION: Increased dietary calcium intake can prevent calcium oxalate stone formation only when the diet is oxalate-rich.