Molka Chaieb

Contribution of type 2 diabetes associated loci in the Arabic population from Tunisia: a case-control study

BackgroundCandidate gene and genome-wide association studies have both reproducibly identified several common Single Nucleotide Polymorphisms (SNPs) that confer type 2 diabetes (T2D) risk in European populations. Our aim was to evaluate the contribution to T2D of five of these established T2D-associated loci in the Arabic population from Tunisia.MethodsA case-control design comprising 884 type 2 diabetic patients and 513 control subjects living in the East-Center of Tunisia was used to analyze the contribution to T2D of the following SNPs: E23K in KCNJ11/Kir6.2, K121Q in ENPP1, the -30G/A variant in the pancreatic β-cell specific promoter of Glucokinase, rs7903146 in TCF7L2 encoding transcription factor 7-like2, and rs7923837 in HHEX encoding the homeobox, hematopoietically expressed transcription factor.ResultsTCF7L2-rs7903146 T allele increased susceptibility to T2D (OR = 1.25 [1.06–1.47], P = 0.006) in our study population. This risk was 56% higher among subjects carrying the TT genotype in comparison to those carrying the CC genotype (OR = 1.56 [1.13–2.16], P = 0.002). No allelic or genotypic association with T2D was detected for the other studied polymorphisms.ConclusionIn the Tunisian population, TCF7L2-rs7903146 T allele confers an increased risk of developing T2D as previously reported in the European population and many other ethnic groups. In contrast, none of the other tested SNPs that influence T2D risk in the European population was associated with T2D in the Tunisian Arabic population. An insufficient power to detect minor allelic contributions or genetic heterogeneity of T2D between different ethnic groups can explain these findings.

Interleukin-10-592C/A, -819C/T and -1082A/G promoter variants affect the susceptibility to nephropathy in Tunisian type 2 diabetes (T2DM) patients.

Background  The Interleukin (IL)‐10 polymorphic variants –1082G/A, –819C/T and –592C/A were linked with obesity, metabolic syndrome, and type 2 diabetes (T2DM). We investigated the hypothesis that IL‐10 promoter polymorphisms may be associated with the progression of diabetic nephropathy (DN).

Predictive value of interleukin-10 promoter genotypes and haplotypes in determining the susceptibility to nephropathy in type 2 diabetes patients.

The IL‐10 promoter polymorphisms ‐1082G/A, ‐819C/T, and ‐592C/A have been consistently associated with type 2 diabetes (T2DM). We examined whether these polymorphisms variants are also associated with progression of diabetic nephropathy (DN).

Identification of specific angiotensin-converting enzyme variants and haplotypes that confer risk and protection against type 2 diabetic nephropathy

Cross‐sectional and family studies identified angiotensin‐converting enzyme (ACE) gene as a risk factor for diabetic nephropathy (DN). The contribution of ACE gene variants to DN development and progression is controversial and varies among different ethnic/racial groups.

Diabetic retinopathy, PAI-1 4G/5G and -844G/A polymorphisms, and changes in circulating PAI-1 levels in Tunisian type 2 diabetes patients.

AIM The association of altered plasminogen activator inhibitor (PAI)-1 levels and PAI-1 polymorphisms (4G/5G and -844G/A) with diabetic retinopathy (DR) was investigated in 856 type 2 diabetes (T2D) patients, of whom 383 presented with (DR group), and 473 presented without (DWR group), retinopathy. METHODS PAI-1 4G/5G and -844G/A genotyping were done by PCR-RFLP, and PAI-1 levels were measured by ELISA testing. RESULTS The genotype distribution of 4G/5G and -844G/A polymorphisms did not deviate from the Hardy-Weinberg equilibrium model among healthy subjects. Higher frequencies of the 4G/4G genotype, and lower frequencies of the -844A allele, -844G/A and -844A/A genotypes, were seen in DR patients, conferring disease susceptibility and protection, respectively. While PAI-1 levels were significantly elevated in the 4G/4G compared with other PAI-1 genotypes, significant differences in PAI-1 levels between DR and DWR patients were seen in the 4G/-844A, 4G/-844G and 5G/-844A haplotype carriers among DR patients. However, comparable distributions of 4G/5G and -844G/A alleles, genotypes and haplotypes, and similar PAI-1 levels, were seen in the proliferative retinopathy (PR) and non-proliferative retinopathy (NPR) patients, indicating that neither PAI-1 variants nor changes in PAI-1 levels were linked to DR severity. Multivariate analyses identified 4G/-844A and 4G/-844G haplotypes as negatively and positively associated, respectively, with DR, but not with DR severity (PR vs NPR) after adjusting for a number of covariates. CONCLUSION The present study identifies changes in PAI-1 levels and genetic variations at the PAI-1 locus as risk factors for DR, but not DR severity, that may serve as useful markers of increased DR susceptibility.

Renin–angiotensin–aldosterone system genotypes and haplotypes affect the susceptibility to nephropathy in type 2 diabetes patients

Background: The association between renin C-4063T and angiotensinogen (AGT) T174M, M235T, and A-6G polymorphisms with diabetic nephropathy (DN) was investigated in Tunisian type 2 diabetes (T2DM) patients. Methods: Study subjects comprised 917 T2DM patients (405 normoalbuminuric, 329 microalbuminuric and 185 macroalbuminuric). Genotyping was done by PCR-RFLP. Results: Renin C-4063T allele and genotype frequencies were comparable between DN cases and normoalbuminuric controls. Although AGT 235T and -6G allele, and 235T/T and -6G/G genotype frequencies were higher in DN compared to normoalbuminuric patients, they were comparable between microalbuminuric or macroalbuminuric patients. Three-locus AGT haplotype analysis (A-6G/T174M/M235T) identified DN-protective (ATM, AMM, GTM) and DN-susceptible (GTM, ATT, GMT and AMT) haplotypes, and demonstrated enrichment of GTT haplotype in macroalbuminuric compared to microalbuminuric or normoalbuminuric patients. Regression analysis confirmed negative (AMM) and positive (GTM, ATT, GMT, AMT) association of AGT haplotypes with microalbuminuria, and negative (AMM) and positive (GTM and ATT) association of AGT haplotypes with macroalbuminuria. None of the AGT haplotypes was associated with DN severity. Conclusions: Genetic variation at the AGT gene influences the risk of nephropathy in T2DM patients but not extent of DN severity, and thus represents a potential DN genetic susceptibility locus worthy of replication.

Association of the peroxisome proliferator-activated receptor-γ2 Pro12Ala but not the C1431T gene variants with lower body mass index in Type 2 diabetes

The peroxisome proliferator-activated receptor-γ (PPARγ) is a nuclear receptor involved in lipid metabolism, adipocyte differentiation and regulation of insulin sensitivity, and is associated with Type 2 diabetes (T2DM). The association of the C1431T silent mutation and the Pro12Ala missense transversion within the PPARY gene with the development of T2DM or obesity has often yielded contradictory results. We examined the association of the PPARY Pro12Ala and C1431T gene variants and their haplotypes with the susceptibility to T2DM. This was a retrospective study involving 491 T2DM patients and 400 age- and gender-matched controls. Pro12Ala and C1431T genotyping was done by PCR-RFLP analysis. Comparable frequencies of the mutant 12Ala (0.07 vs 0.08, p=0.216) and 1431T (0.12 vs 0.10, p=0.189) alleles, and Pro12Ala (p=0.218) and C1431T (p=0.421) genotypes were seen between patients and in non-diabetic control subjects. While no difference was noted in the distribution of Pro12Ala-C1431T haplotypes and genotypes between patients and controls, the PPARY 12Ala, but not 1431T, allele was significantly associated with lower body mass index (BMI) (≤25.0) among patients. Regression analysis confirmed the association of the Pro12Ala (odds ratio =5.340; 95% confidence interval =1.044-27.311) with normal (BMI<25.0) but not with overweight/obesity among T2DM patients. Despite its association with lower BMI among T2DM patients, the PPARY gene does not appear to markedly influence Type 2 diabetes among Tunisian subjects.

Analysis of FMR1 gene premutation and X chromosome cytogenetic abnormalities in 100 Tunisian patients presenting premature ovarian failure

OBJECTIVE To evaluate the prevalence of FMR1 premutations and X chromosome cytogenetic abnormalities in a large cohort of Tunisian women with premature ovarian failure (POF). PATIENTS AND METHODS The cohort consisted of 127 Tunisian women with POF referred by endocrinologists and gynecologists for genetic investigation in the context of idiopathic POF and altered hormonal profiles. Clinical information concerning the reproductive function in the family, previous hormonal measurements and/or possible fertility treatment were collected. Karyotype, FISH analyses, FMR1 and FMR2 testing were performed for all patients. RESULTS Fifteen patients (11.81%) presented structural or numerical X chromosomal abnormalities. Moreover, we detected in 12 patients (10.71%) a high level of X mosaicism. Analysis of FMR1 gene in the 100 patients without X chromosomal abnormalities showed that five percent of the patients carried a FMR1 premutation allele. On the other hand, the FMR2 screening did not reveal any deletion. CONCLUSION Our study confirms the major role of X chromosome abnormalities in POF and highlights the importance of karyotype analyses and FMR1 screening. These investigations provide valuable information for diagnosis and genetic counseling for these women who still have a 5% chance of spontaneous conception.

Diabète de type 1 post-traumatique chez un soldat de l’armée

The influence of stress as a precipitating factor associated with the onset of type 1 diabetes have been widely studied in the literature. The relationship between physical and psychological traumas and diabetes has been rarely studied in the military environment. Posttraumatic diabetes is a controversial topic. We here report the case of a Tunisian soldier, with no previous medical and family history of autoimmune disease who was diagnosed with Type 1 diabetes after a physical aggression occurred during a social conflict between the forces of law and order and the citizens.

Etude sur le diabète aigu cétosique inaugural dans un hôpital du Centre-Est Tunisien

La cétose est une complication aiguë du diabète qui consiste en une accumulation de corps cétoniques sanguins. Malgré la haute prévalence du diabète cétosique décrite, il existe très peu d’informations concernant l’épidémiologie de cette complication inaugurale du diabète en Tunisie. L’objectif était de déterminer les caractéristiques épidémiologiques et clinico-biologiques des cétoses inaugurales dans un hôpital du Centre-Est tunisien. Il s’agit d’une étude rétrospective, transversale et exhaustive, à propos de patients admis pour une cétose inaugurale sur une période allant de janvier 2010 à août 2016. La population d’étude a été divisée en 2 groupes selon la présence ou pas d’une auto-immunité anti pancréatique: groupe DAI (diabète de type 1 auto-immun) regroupe tous les patients avec une auto-immunité, et le groupe DNAI (diabète cétosique non auto-immuns) sans auto-immunité. Il s’agit de 391 patients, de sex ratio 266 hommes/125 femmes, d’âge moyen de 34±14,33 ans. La prédominance masculine était nette: 68% dans la population générale. L’âge de la cétose était significativement plus précoce dans le groupe DAI. Un facteur précipitant la cétose était retrouvé chez 77,7% de la population globale d’étude, significativement plus fréquent dans le groupe DAI que dans le groupe DNAI. Le facteur le plus retrouvé était les infections virales. Les Anticorps anti thyroïdiens étaient significativement importants dans le groupe DAI. La cétose est un facteur de décompensation inaugurale fréquent du diabète en Tunisie. La population la plus importante a été décrite chez l’adulte jeune masculin, avec l’absence d’une auto-immunité, et un profil clinique du diabète de type 2.