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.

Screening for Nephropathy in Diabetes Mellitus: Is Micral-Test Valid among All Diabetics?

Background. Using Micral-test (MT) for screening microalbuminuria (MA) among type 2 diabetics (T2D) is helpful. We aimed at determining prevalence of MA and at describing the MT validity. Methods. We studied 182 T2D followed up in family medicine. Two 24-hour urinary quantitative assays of MA had been used as a gold standard. Results. Prevalence of MA was 23%, CI 95%: 16.9-29.1. MT validity was 77% for sensitivity, 88% for negative predictive value, and 0.2 for Kappa coefficient (p = 0.001). Among subjects having a blood pressure ≥130/80 mmHg, having a CHT/HDL ratio ≥ 3, being a T2D for more than 5 years, and being women, negative predictive values were, respectively, 91%, 89%, 95%, and 91%. The area under the ROC curve was 0.81 in men (p = 0.008) and 0.80 when diabetes duration exceeds 5 years (p = 0.001). The MA value at 100% Sp for MT was 35 mg/L. Conclusion. The use of MT in primary healthcare for yearly screening for MA in T2D must be accentuated especially when diabetes duration exceeds 5 years or when associated with other cardiovascular risks.

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.

A Pro 12 Ala substitution in the PPARγ2 polymorphism may decrease the number of diseased vessels and the severity of angiographic coronary artery.

AIMS: Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated transcription factor that regulates the gene expression of the key proteins involved in lipid metabolism, vascular inflammation, and proliferation. PPARγ may contribute toward attenuation of atherogenesis. We investigated the relationship of the Pro 12 Ala PPARγ2 polymorphism with the presence and severity of coronary artery disease (CAD) assessed by Gensini score (Gs). MATERIALS AND METHODS: A total of 239 patients and 244 control individuals were investigated for clinical, biochemical, anthropometric, and angiographic information. Standard definitions were used to diagnose patients with acute coronary syndrome. The Gs system was used to calculate the severity of CAD. The computer model Homeostatic Model Assessment (HOMA) 2 was used to determine ß-cell function (HOMA-ß), insulin sensitivity (HOMA-S), and insulin resistance (HOMA-IR). PCR-RFLP was performed for DNA genotyping for Pro 12 Ala in the PPARγ2 polymorphism. RESULTS: Allele frequencies were 0.842 for the Pro allele and 0.158 for the Ala allele. The diseased vessel number was lower in patients with the Ala allele than others. The Gs tended to be lower in patients with the Ala allele than in others [10 (8-16) vs. 24 (16-32), P<0.001]. Patients with Pro/Pro had a significantly higher glycemia, insulinemia, and HOMA-IR, and reduced HOMA-ß and HOMA-S than Pro/Ala and Ala/Ala individuals. CONCLUSION: The Ala 12 Ala genotype of the PPARγ2 gene may decrease the number of diseased vessels and the severity of CAD, which could be because of a direct antiatherogenic effect of this polymorphism as well as an indirect effect through its association with a lower level of inflammatory parameters and insulin resistance.

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.