Noura Bougacha-Elleuch

TNF gene polymorphisms in Graves’ disease: TNF-308 A/G meta-analysis

Autoimmune thyroid diseases (AITDs), including Graves’ disease (GD) and Hashimoto thyroiditis, are associated with human MHC polymorphisms. The present study analysed two polymorphisms within tumour necrosis factor (TNF) genes (TNF-308 A/G SNP and TNFb (CT)n microsatellite) in a sample of 106 GD patients and 199 controls from the Tunisian population. The present study was designed to investigate genetic association of these polymorphisms (taken separately or considered as a haplotype) with GD development. Statistical analysis confirmed the association between the TNF-308 A allele and GD (p=0.002), previously reported in a Tunisian familial study. The data from the present study suggest that the TNF-308 A allele plays a role in GD pathogenesis in the Tunisian population. This association was further confirmed by a meta-analysis on eight published studies (p<0.0001). Haplotype analysis with GD revealed an associated haplotype (TNFb3–TNF-308 G haplotype: c=13.16; p=0.0003).

No major genes in autoimmune thyroid diseases: complex segregation and epidemiological studies in a large Tunisian pedigree

1Unité Cibles pour le Diagnostic et la Thérapie, Centre de Biotechnologie Sfax, BP ‘1177’ 3018, Universiteé de Sfax, Sfax, Tunisia 2Unité d’ Epidémiologie Génétique et Moléculaire, Faculté de Médecine de Tunis, La Rabta-1007 Bab Saâdoun Tunis, Tunisia 3Unité de Bioinformatique, Centre de Biotechnologie Sfax, BP ‘1177’ 3018, Sfax, Tunisia 4Service Endocrinologie, CHU Hédi Chaker, Route el Ain, 3000, Sfax, Tunisia 5Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine, Sfax, Avenue Majida Bou Leila 3029, Sfax, Tunisia 6Cabinet d’Endocrinologie, Sfax, Avenue Majida Bou Leila 3029, Sfax, Tunisia 7Dispensaire Bir Hfay, 24005, Sidi Bouzid, Tunisia

Potential Predictive Role of Lipid Peroxidation Markers for Type 2 Diabetes in the Tunisian Population

OBJECTIVES We evaluated the potential clinical relevance of malondialdehyde (MDA) and autoantibodies to copper oxidized low-density lipoprotein (CuOx-LDL) in type 2 diabetes occurrence. METHODS This cross-sectional study enrolled 69 normoglycemic subjects, 18 prediabetic patients and 108 type 2 diabetes patients. MDA concentration was assessed spectrophotometrically. Plasma IgG, IgA and IgM levels to CuOx-LDL were determined by ELISA. RESULTS Plasma MDA levels were considerably higher in obese, prediabetic and type 2 diabetes subjects compared to controls. In multiple linear regression analysis, both MDA and IgA to CuOx-LDL were significantly associated with glucose metabolism markers (p<0.05). Multiple logistic regression analyses showed that high plasma MDA and IgA to CuOx-LDL were independent risk factors for type 2 diabetes (OR 1.196, 95% CI: 1.058 to 1.353; p=0.004; OR 1.626, 95% CI: 1.066 to 2.481; p=0.024; respectively). Importantly, elevated IgA to CuOx-LDL predicted incident diabetes in patients with prediabetes (OR 2.321, 95% CI:1.063 to 5.066; p=0.035). From stratified analyses by body mass index (BMI), both MDA and IgA to CuOx-LDL remained independent predictors of type 2 diabetes occurrence in non-obese subjects (p<0.05). More interesting, elevated IgA to CuOx-LDL levels could be predictors of type 2 diabetes in obese prediabetic subjects (p=0.044). Conversely, neither IgG nor IgM to CuOx-LDL was associated with glucose metabolism markers, obesity or type 2 diabetes. CONCLUSIONS Plasma MDA and IgA to CuOx-LDL were significantly associated with blood markers of glucose metabolism. High levels of MDA and IgA to CuOx-LDL could independently predict type 2 diabetes development in normoglycemia and prediabetic subjects.

Affinity kinetics of leptin-reactive immunoglobulins are associated with plasma leptin and markers of obesity and diabetes

Obese subjects display elevated plasma levels of leptin reflecting the phenomenon of leptin resistance. Here, we aimed to determine whether leptin-reactive immunoglobulins (Ig) are present in obese and type 2 diabetes (T2D) patients and whether their plasma levels and affinity kinetics may correlate with obesity and diabetes markers. We show that leptin levels are increased in obese patients with and without T2D. Although mean plasma levels of leptin-reactive IgG were similar between study groups, IgG in obese non-diabetic patients had increased dissociation rate and lower affinity (increased dissociation equilibrium constant value; KD). In controls and diabetic patients, the association rates of leptin IgG correlated negatively with obesity and diabetes markers, respectively. In contrast, KD values correlated positively with plasma leptin levels and obesity traits in our cohort, and with diabetes markers in both the total cohort and in the obese T2D group. Taken together, our data reveal that leptin-reactive IgG are present in healthy subjects, obese, and diabetic patients but display altered affinity kinetics in obesity. Increased IgG binding to leptin in healthy subjects associated with lower body mass index (BMI) suggests an enhancing role of IgG in leptin signaling. Accordingly, a decreased affinity of IgG for leptin, found in obese patients, can be relevant to leptin resistance.

Erratum to: Segregation of S292F TPO gene mutation in three large Tunisian families with thyroid dyshormonogenesis: evidence of a founder effect

1 Unité Cibles pour le Diagnostic et la Thérapie, Centre de Biotechnologie Sfax, BP 1177, 3018 Sfax, Tunisia 2 Service d’Endocrinologie, CHU Hédi Chaker, Sfax, Tunisia 3 Laboratoire de Biochimie et de Génie Enzymatique des Lipases, Ecole Nationale d’Ingénieurs de Sfax, Route Soukra BP W, Sfax, Tunisia 4 Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine, Sfax, Tunisia 5 Unidade de Genética Molecular, Centro de Genética Médica Doutor Jacinto Magalhães, Centro Hospitalar do Porto, Porto, Portugal 6 Unit for Multidisciplinary Research in Biomedicine, UMIB, ICBASUP, Porto, Portugal 7 Service de Pédiatrie, CHU Hédi Chaker, Sfax, Tunisia Eur J Pediatr (2015) 174:1703 DOI 10.1007/s00431-015-2669-3