Gut microbiota profile and the influence of nutritional status on bacterial distribution in diabetic and healthy Tunisian subjects.

Gut microbiota plays a key role in the regulation of metabolism and immunity. We investigated the profile of gut microbiota and the impact of dietary intake on gut bacterial distribution in diabetic and healthy Tunisian subjects, aiming to identify a dysbiotic condition, hence opening the way to restore eubiosis and facilitate return to health. In the present research, we enrolled 10 type 1 diabetic (T1D), 10 type 2 diabetic (T2D) patients and 13 healthy (H) subjects. Illumina Miseq technology was used to sequence V3-V4 hypervariable regions of bacterial 16SrRNA gene. Data were analyzed referring to QIIME 2 pipeline. RStudio software was used to explore the role of nutrition in gut bacterial distribution. At the phylum level, we identified an imbalanced gut microbiota composition in diabetic patients marked by a decrease in the proportion of Firmicutes and an increase in the abundance of Bacteroidetes compared with H subjects. We observed higher amounts of Fusobacteria and a decline in the levels of TM7 phyla in T1D patients compared with H subjects. However, we revealed a decrease in the proportions of Verrucomicrobia in T2D patients compared with H subjects. At the genus level, T2D subjects were more affected by gut microbiota alteration, showing a reduction in the relative abundance of Faecalibacterium, Akkermansia, Clostridium, Blautia and Oscillibacter, whereas T1D group shows a decrease in the proportion of Blautia. The gut bacteria distribution was mainly affected by fats and carbohydrates consumption. Gut microbiota composition was altered in Tunisian diabetic patients and affected by dietary habits.

Prevalence and risk factors of diabetes mellitus and hypertension in North East Tunisia calling for efficient and effective actions.

Diabetes and hypertension are a serious public health problem worldwide. In the last decades, prevalence of these two metabolic diseases has dramatically increased in the Middle East and North Africa region, especially in Tunisia. This study aimed to determine the prevalence of type 2 diabetes (T2D) and High Blood Pressure (HBP) in Zaghouan, a North-East region of Tunisia. To this end, an exploratory study with stratified random sampling of 420 participants has been carried out. Various data were collected. Blood samples and urine were drawn for biochemical assay. Then, all data were analyzed using the statistical R software. Results showed an alarming situation with an inter-regional difference in prevalence of obesity (50.0%, CI 95.0%), HBP (39.0%, CI 95.0%) and T2D (32.0%, CI 95.0%). This study allowed the discovery of 24, 17 and 2 new cases of T2D, HBP and T2D&HBP respectively. The association of some socio-economic factors and biochemical parameters with these chronic diseases has been highlighted. To conclude, the health situation in the governorate of Zaghouan requires urgent interventions to better manage the growing epidemic of non-communicable diseases (NCD) in the region. This study demonstrated the importance of engaging health policy makers in road mapping and implementing national NCD prevention programs.

The first exome wide association study in Tunisia: identification of candidate loci and pathways with biological relevance for type 2 diabetes.

Introduction: Type 2 diabetes (T2D) is a multifactorial disease involving genetic and environmental components. Several genome-wide association studies (GWAS) have been conducted to decipher potential genetic aberrations promoting the onset of this metabolic disorder. These GWAS have identified over 400 associated variants, mostly in the intronic or intergenic regions. Recently, a growing number of exome genotyping or exome sequencing experiments have identified coding variants associated with T2D. Such studies were mainly conducted in European populations, and the few candidate-gene replication studies in North African populations revealed inconsistent results. In the present study, we aimed to discover the coding genetic etiology of T2D in the Tunisian population. Methods: We carried out a pilot Exome Wide Association Study (EWAS) on 50 Tunisian individuals. Single variant analysis was performed as implemented in PLINK on potentially deleterious coding variants. Subsequently, we applied gene-based and gene-set analyses using MAGMA software to identify genes and pathways associated with T2D. Potential signals were further replicated in an existing large in-silico dataset, involving up to 177116 European individuals. Results: Our analysis revealed, for the first time, promising associations between T2D and variations in MYORG gene, implicated in the skeletal muscle fiber development. Gene-set analysis identified two candidate pathways having nominal associations with T2D in our study samples, namely the positive regulation of neuron apoptotic process and the regulation of mucus secretion. These two pathways are implicated in the neurogenerative alterations and in the inflammatory mechanisms of metabolic diseases. In addition, replication analysis revealed nominal associations of the regulation of beta-cell development and the regulation of peptidase activity pathways with T2D, both in the Tunisian subjects and in the European in-silico dataset. Conclusions: The present study is the first EWAS to investigate the impact of single genetic variants and their aggregate effects on T2D risk in Africa. The promising disease markers, revealed by our pilot EWAS, will promote the understanding of the T2D pathophysiology in North Africa as well as the discovery of potential treatments.

Association of HNF1A gene variants and haplotypes with metabolic syndrome: a case-control study in the Tunisian population and a meta-analysis.

BACKGROUND: Variants in the Hepatocyte Nuclear Factor 1 Alpha gene (HNF1A) are associated with lipoproteins levels and type 2 diabetes. In this study, we aimed to assess the association of HNF1A gene and haplotypes with the metabolic syndrome (MetS) and its components through an association study in the Tunisian population as well as by a meta-analysis. METHODS: A total of 594 Tunisian individuals were genotyped for three variants (rs1169288, rs2464196 and rs735396) located in HNF1A gene using KASPar technology. Statistical analyses were performed with R software. The association was furthermore evaluated through a meta-analysis of our results with those obtained in a Moroccan population. RESULTS: Our results showed no association between HNF1A variants and MetS in the Tunisian population. However, a significant association was observed between the variant rs735396 and a higher waist circumference. The stratified analysis according to the sex highlighted a significant association between the variant rs1169288 and high cholesterol levels only in women. Similarly, Haplotype analysis showed an association between the HNF1A minor haplotype and high total cholesterol mainly in women. Finally, our meta-analysis showed no association between HNF1A variants and MetS. CONCLUSIONS: Our findings exclude the involvement of the three HNF1A variants rs1169288, rs2464196 and rs735396 in the susceptibility to MetS in our studied Tunisian population but emphasize the role of these variants in the cholesterol homeostasis with sex-specific differences, which may serve to rise clinical consideration to early statin therapy in women carrying these genetic variants.

Association of rs662799 variant and APOA5 gene haplotypes with metabolic syndrome and its components: a meta-analysis in North Africa.

Apolipoprotein A5 (APOA5) has been linked to metabolic syndrome (MetS) in several populations. In North Africa, only the Tunisian and Moroccan populations were investigated. Our aim is to assess the association between APOA5 gene variant (rs662799) and haplotypes with MetS in Tunisian population and to perform a meta-analysis in North Africa. A total of 594 Tunisian participants were genotyped for polymorphism rs662799 using KASPar technology. Two polymorphisms rs3135506 and rs651821 in APOA5 gene genotyped in our previous study, were used in addition to rs662799 to assess the haplotype association with MetS. The genotype of 875 participants was used for the meta-analysis. Statistical analyses were performed with R software. The rs662799 increases the risk of MetS under the dominant (P=0.018) and the additive models (P=0.028) in the Tunisian population. After stratification of the cohort following the sex and the geographic origin, a positive association of rs662799 with MetS was found for participant from the Northern region and for the women group. Only the haplotype AGT showed a significant association with MetS by decreasing the risk of the disease. The meta-analysis reported a significant association of rs662799 and rs3135506 with MetS. Our results showed a significant association between the APOA5 gene variants rs662799 and haplotypes with MetS and its traits in Tunisia. An impact of the sex and the geographic origin on the genotype distribution was highlighted. Our funding emphasizes the role of APOA5 in the development of MetS in North Africa.

Gut microbiota imbalances in Tunisian participants with type 1 and type 2 diabetes mellitus.

Gut microbiota plays an important role in the regulation of the immune system and host's metabolism. We aimed to characterize the gut microbiota of Tunisian participants with and without diabetes.We enrolled ten participants with type 1 diabetes mellitus (T1DM), ten patients with type 2 diabetes mellitus (T2DM), and 11 subjects without diabetes. Bacteria was quantified in fecal samples by quantitative PCR (qPCR). Statistical tests and multivariate analysis were performed using RStudio program.Results showed that the proportions of Firmicutes, Akkermansia muciniphila, and Faecalibacterium prausnitzii (P≤0.041), as well as, the ratio Firmicutes/Bacteroidetes decreased in participants with T1DM compared with those without diabetes (p = 0.036). Participants with T2DM presented a reduction in the amounts of A. muciniphila and F. prausnitzii compared with those without diabetes (P≤0.036). Furthermore, A. muciniphila is negatively correlated with glucose level (P=0.022) and glycated hemoglobin (HbA1c) (P=0.035). Multivariate analysis revealed that participants with diabetes formed a cluster apart compared with those without diabetes.In conclusion the gut bacteria of Tunisian participants with diabetes was altered. The gut bacterial profile, especially the distribution of A muciniphila in participants with diabetes was affected by glycemic dysregulation. The investigation of the gut microbiota may help clinicians to improve diagnosis and treatment of diabetes and its complications.

Genetic characterization of suspected MODY patients in Tunisia by targeted next-generation sequencing.

AIMS: Maturity Onset Diabetes of the Young (MODY) is a monogenic form of diabetes with autosomal dominant inheritance pattern. The diagnosis of MODY and its subtypes is based on genetic testing. Our aim was investigating MODY by means of next-generation sequencing in the Tunisian population. METHODS: We performed a targeted sequencing of 27 genes known to cause monogenic diabetes in 11 phenotypically suspected Tunisian patients. We retained genetic variants passing filters of frequency in public databases as well as their probable effects on protein structures and functions evaluated by bioinformatics prediction tools. RESULTS: Five heterozygous variants were found in four patients. They include two mutations in HNF1A and GCK that are the causative genes of the two most prevalent MODY subtypes described in the literature. Other possible mutations, including novel frameshift and splice-site variants were identified in ABCC8 gene. CONCLUSIONS: Our study is the first to investigate the clinical application of targeted next-generation sequencing for the diagnosis of MODY in Africa. The combination of this approach with a filtering/prioritization strategy made a step towards the identification of MODY mutations in the Tunisian population.

Pharmacogenetic landscape of Metabolic Syndrome components drug response in Tunisia and comparison with worldwide populations.

Genetic variation is an important determinant affecting either drug response or susceptibility to adverse drug reactions. Several studies have highlighted the importance of ethnicity in influencing drug response variability that should be considered during drug development. Our objective is to characterize the genetic variability of some pharmacogenes involved in the response to drugs used for the treatment of Metabolic Syndrome (MetS) in Tunisia and to compare our results to the worldwide populations. A set of 135 Tunisians was genotyped using the Affymetrix Chip 6.0 genotyping array. Variants located in 24 Very Important Pharmacogenes (VIP) involved in MetS drug response were extracted from the genotyping data. Analysis of variant distribution in Tunisian population compared to 20 worldwide populations publicly available was performed using R software packages. Common variants between Tunisians and the 20 investigated populations were extracted from genotyping data. Multidimensional screening showed that Tunisian population is clustered with North African and European populations. The greatest divergence was observed with the African and Asian population. In addition, we performed Inter-ethnic comparison based on the genotype frequencies of five VIP biomarkers. The genotype frequencies of the biomarkers rs3846662, rs1045642, rs7294 and rs12255372 located respectively in HMGCR, ABCB1, VKORC1 and TCF7L2 are similar between Tunisian, Tuscan (TSI) and European (CEU). The genotype frequency of the variant rs776746 located in CYP3A5 gene is similar between Tunisian and African populations and different from CEU and TSI. The present study shows that the genetic make up of the Tunisian population is relatively complex in regard to pharmacogenes and reflects previous historical events. It is important to consider this ethnic difference in drug prescription in order to optimize drug response to avoid serious adverse drug reactions. Taking into account similarities with other neighboring populations, our study has an impact not only on the Tunisian population but also on North African population which are underrepresented in pharmacogenomic studies.

Orosensory detection of bitter in fat-taster healthy and obese participants: Genetic polymorphism of CD36 and TAS2R38.

BACKGROUND & AIMS: We assessed orosensory detection of a long-chain fatty acid, linoleic acid (LA), and a bitter taste marker, 6-n-propylthiouracil (PROP), and correlated lipid-taster subjects with PROP detection and polymorphism in genes encoding bitter and lipid taste receptors, respectively, TAS2R38 and CD36, in normal weight and obese subjects. DESIGN: The normal weight (n = 52, age = 35.3 ± 4.10 years, BMI = 23.22 ± 1.44 kg/m2) and obese (n = 52, age = 35.0 ± 5.43 years, BMI = 34.29 ± 5.31 kg/m2) participants were recruited to determine fat and bitter detection thresholds. The genomic DNA was used to determine single nucleotide polymorphism (SNP) of CD36 (rs1761667) and TAS2R38 (rs1726866 and rs10246939). RESULTS: The study included the participants who could detect LA, i.e., lipid-tasters. There was a positive correlation between BMI and detection thresholds for fat and bitter taste in normal weight and obese subjects. Obese participants showed a positive correlation between LA and PROP detection thresholds. PROP detection thresholds were higher for CD36 SNP (rs1761667) and TAS2R38 SNPs (rs1726866 and rs10246939) in obese participants compared to normal weight subjects. LA detection thresholds were not high for CD36 SNP (rs1761667) or TAS2R38 SNP (rs1726866 and rs10246939) in obese participants. CONCLUSIONS: Orosensory detection thresholds for fat and bitter taste are associated with BMI, and CD36 and TAS2R38 genotypes are not always associated with taste phenotypes.

Lactase persistence in Tunisia as a result of admixture with other Mediterranean populations.

BACKGROUND: The ability to digest lactose after weaning, namely, lactase persistence (LP), is encoded by polymorphisms in the MCM6 gene and varies widely in frequency among different human populations. Although, evolution of LP-related genetic variants was investigated in many groups of Sub-Saharan African, Middle Eastern, and European ancestry, only few studies have focused on populations from North Africa and no data are especially available from the Tunisian one. For this reason, there is an urgent need to investigate the frequency patterns at these loci in Tunisia since this adaptive trait is implicated in health. METHODS: Forty SNPs covering the LCT/MCM6 genes and including the two functional variants - 13,910 C > T and - 22,018 G > A were genotyped in 117 Tunisian individuals using the Sequenom Mass Array technology. The observed nucleotide and haplotype patterns of variation were then compared with those of several African, European, and Mediterranean human groups for which comparable data were publicly available. Admixture analysis on a 5 Mb genomic region surrounding the LCT/MCM6 loci was also performed by extracting genotypes from a previously generated genome-wide dataset in order to deepen the reconstruction of the evolutionary history of these loci. RESULTS: We found that lactase non-persistence (LNP)-related alleles and haplotypes were predominantly present in the examined population. A clear differentiation between Tunisian, African, and North European/North Italian samples was found, while the Tunisian population showed more genetic affinity to Central and South Italian groups. CONCLUSIONS: Our study provided a first report of LP-associated alleles and haplotypes in the Tunisian population. We highlighted a gradient followed by LP diffusion from Europe to North Africa. Based on the rich historic background of Tunisia, we suggest that this adaptive trait was introduced in that geographic region by a relatively recent gene flow.

Association of apolipoprotein A5 gene variants with metabolic syndrome in Tunisian population.

AIM OF THE STUDY: APOA5 has been linked to metabolic syndrome (MetS) or its traits in several populations. In North Africa, only the Moroccan population was investigated. Our aim is to assess the association between APOA5 gene polymorphisms with the susceptibility to MetS and its components in the Tunisian population. MATERIALS AND METHODS: A total of 594 participants from the Tunisian population were genotyped for two polymorphisms rs3135506 and rs651821 located in APOA5 gene using KASPar technology. Statistical analyses were performed using R software. RESULTS: The SNP rs651821 increased the risk of MetS under the dominant model (OR=1.91 [1.17-3.12], P=0.008) whereas the variant rs3135506 was not associated with MetS. After stratification of the cohort following the sex, only the variant rs651821 showed a significant association with MetS among the women group. The influence of the geographic origin of the studied population on the genotype distribution of APOA5 variants showed that the variant rs651821 was significantly associated with MetS only for the Northern population. The association analyses of the variants rs651821 and rs3135506 with different quantitative traits of MetS showed a significant association only between the variant rs3135506 and triglycerides levels. CONCLUSION: This is the first study reporting the association of APOA5 gene variants with MetS in Tunisia. Our study emphasizes the role of APOA5 variants in the regulation of the triglycerides blood levels. Further studies are needed to confirm the clinical relevance of these associations and to better understand the physiopathology of the MetS.

Depression in Tunisian type 2 diabetic patients: prevalence and association to glycemic control and to treatment compliance.

AIM: to study the prevalence of depression in type 2 diabetes and to seek for a relationship between glycemic control and treatment adherence. METHODS: This cross-sectional study was carried out at the outpatient department of the Tunis nutrition institute. A total of 100 diabetic patients followed for Type 2 diabetes were randomly recruited. We used a structured questionnaire to collect patients' socio-demographic, clinical and therapeutic data. The treatment adherence was assessed by using MAS, Glycemic control according to blood glucose and glycated hemoglobin (HbA1c) levels and depression and anxiety by administering a dialectal Arabic validated version of Hospital Anxiety and Depression Scale (HAD). Finaly we also used the modules on mood disorders of the mini international neuropsychiatric interview (MINI). RESULTS: The prevalence of depression in T2DP was 38% according to the HAD scale with severe forms in 18%. The anxiety prevalence was 31%. However, 18% of T2DP had anxious-depressive co morbidity. According to the MINI, 31% of T2DP had a mood disorder. Dysthymia was noted in 14% of cases, an isolated depressive episode in 6%. Depressed T2DP have a poor glycemic control than those no depressed. Macro-angiopathy, irregular followed-up, poor treatment adherence and unbalanced diet were associated with depression. CONCLUSION: The detection of depression related to somatic pathology in particular diabetes, seems essential. As a result, depression treatment may improve the overall prognosis of the associated somatic diseases.

Gender-specific associations of genetic variants with metabolic syndrome components in the Tunisian population.

AIM OF THE STUDY: Recent genome-wide association studies (GWASs) have identified many genetic variants associated with metabolic syndrome (MetS). However, their contribution to MetS in ethnic groups in Tunisia is largely unexplored. In this study, we aim to examine the associations of related loci with a risk of metabolic syndrome in a sample of Tunisians. MATERIALS AND METHODS: Overall seven polymorphisms rs7265718, rs10401969, rs762861, rs12310367, rs1562398, rs2059807, rs4420638 located at C20orf152, CILP2, LRPAP1, ZNF664, KLF14, INSR, APOE, respectively, were analyzed in 356 samples from the Tunisian population. Anthropometric and biochemical parameters were assessed. Metabolic syndrome was defined according to the International Diabetes Federation (IDF). RESULTS: We find that LRPAP1-rs762861 C allele increases susceptibility to MetS (OR = 1.39, 95% CI = 0.99-1.95, p = 0.041). Separate analysis in men and women revealed the association of rs762861 among females (OR = 1.6, 95% CI = 1.057-2.41, p = 0.021), but not among males (OR = 0.953, 95% CI = 0.51-1.78, p = 0.882). ZNF664-rs12310367 was also found to be associated with body mass index (BMI) in women (p = 0.01) and not in men (p = 0.18). KLF14-rs1562398 was significantly correlated with impaired fasting glucose (p = 0.004) only in men. CONCLUSIONS: Our results reveal new candidate genes for MetS in the Tunisian population and suggest that the genetic basis of this syndrome is gender dependent. Further studies are necessary to understand why these associations differ between males and females.

Association of rs9939609 Polymorphism with Metabolic Parameters and FTO Risk Haplotype Among Tunisian Metabolic Syndrome.

BACKGROUND: Variants in the fat mass and obesity-associated (FTO) gene are associated with obesity and type 2 diabetes mellitus. AIM OF THE STUDY: This study aims to assess the association of the rs9939609 variant and haplotypes in FTO gene with metabolic syndrome (MetS) components in a Tunisian population sample. METHODS: A total of 685 Tunisian subjects were genotyped for the rs9939609T>A using TaqMan allelic discrimination assay. Two variants rs1421085T>C and rs8057044A>G already genotyped in a previous study were used to test haplotype association of the FTO gene. RESULTS: Genotype distribution of the variant rs9939609 was different between MetS and controls (P = 0.017). Individuals carrying TA genotypes had a significantly increased risk independently of body mass index or age (P = 0.009). The variant rs9939609 was also associated with impaired fasting glucose (IFG) (P = 0.002). Among the eight haplotypes in the population, the haplotype GCA was significantly associated with a higher risk of developing the MetS, higher systolic blood pressure, and higher levels of fasting glucose and triglycerides (TGs) in the total sample and females, separately. Separate analysis by gender revealed a protective haplotype TGT among women (P = 0.023). CONCLUSIONS: FTO haplotypes have a strong influence on blood pressures and TG and IFG levels. These findings provide evidence that FTO gene may play a critical role in leading to MetS in Tunisian population.

Study of the T16189C variant and mitochondrial lineages in Tunisian and overall Mediterranean region.

The mitochondrial DNA (mtDNA) variant T16189C has been investigated in several metabolic diseases. In this study, we aimed to estimate the frequency of the T16189C variant in Tunisian and other Mediterranean populations and to evaluate the impact of this variant on the phylogeny of Mediterranean populations. Blood sample of 240 unrelated Tunisian subjects were recruited from several Tunisian localities. The hypervariable region 1 of the mtDNA were amplified and sequenced. Additional sequences (N = 4921) from Mediterranean populations were compiled from previous studies. The average frequency of T16189C variant in Tunisia (29%) is similar to that observed in North African and Near Eastern populations. Our findings showed positive correlation of the T16189C variant with Sub-Saharan and North African lineages, while a negative correlation was found with the Eurasian haplogroups, reaching its maximum with the Eurasian haplogroup H. The principal component analyses showed a high internal heterogeneity between Tunisian localities. At the Mediterranean scale, Tunisians are closer to North African (Algerian and Moroccan) and Near Eastern populations (Syrians and Palestinians) than to Europeans.

Association of genetic variants in the FTO gene with metabolic syndrome: A case-control study in the Tunisian population.

AIMS: Variants in the fat mass and obesity-associated gene (FTO) are associated with obesity and type 2 diabetes. However, the association of FTO variants in the MENA (Middle East and North Africa) region with MetS is largely unknown. In this study, we aimed to investigate the association of FTO gene with MetS and its components in Tunisian population. METHODS: Two variants in the FTO gene were genotyped: rs1421085 T>C and rs8057044 A>G in cases and controls from Tunisian population. Anthropometric and biochemical parameters were assessed. Metabolic syndrome was defined according to the International Diabetes Federation (IDF). RESULTS: The FTO rs1421085 variant conferred an increased risk to MetS (OR=1.61, 95% CI=1.14-2.26, P=0.024) that was abolished when adjusted for fasting plasma glucose (FPG), suggesting that the association may be due to variation in FPG levels. Indeed, this variant was associated to FPG (OR = 1.7, 95% CI=1.23-2.44, P=0.002) independently from BMI or age. The second polymorphism rs8057044 was associated with high blood pressure levels (OR=1.45, 95% CI=1.06-1.99, P=0.019). CONCLUSIONS: This is the first study highlighting the association between FTO gene variants and MetS in Tunisian population. These findings provide evidence that FTO gene may play a critical role in leading to MetS in Tunisian population.

Association study of mitochondrial DNA polymorphisms with type 2 diabetes in Tunisian population.

Mitochondrial DNA (mtDNA) variation may play an important role in the pathogenesis of type 2 diabetes (T2Ds). In this study, we aimed to explore whether mtDNA variants contribute to the susceptibility to T2Ds in a Tunisian population. The hypervariable region 1 (HVS1) of the mtDNA of 64 T2Ds patients and 77 healthy controls was amplified and sequenced. Statistical analysis was performed using the STATA program. Analysis of the total screened variants (N = 88) from the HVS1 region showed no significant difference in the distribution of all polymorphisms between T2Ds and controls, except for the variant G16390A which was more frequent in T2Ds (15.9%) than in controls (5.4%) (p = 0.04). The association of G16390A was not detected after multivariate regression analysis. Similarly, analysis of the distribution of mitochondrial haplogroups within our dataset showed 18 distinct major haplogroups with no significant difference between T2Ds and controls. Except, the weakly association found for the G16390A variant, our results showed that none of the tested polymorphisms from the HVS1 region have a major role in T2Ds pathogenesis in the studied Tunisian population even when taking into account the population stratification.

Contribution of CDKAL1 rs7756992 and IGF2BP2 rs4402960 polymorphisms in type 2 diabetes, diabetic complications, obesity risk and hypertension in the Tunisian population.

BACKGROUND: The insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) and the cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 (CDKAL1) identified through genome-wide association (GWA) studies have been shown to be associated with Type 2 diabetes in various ethnic groups. In this study, we investigated the association of the rs7756992 of CDKAL1 and the rs4402960 of IGF2BP2 with Type 2 diabetes, diabetic complications (nephropathy, retinopathy and cardiovascular disease), obesity and hypertension in a Tunisian population. METHODS: A case-control association study including 200 Type 2 diabetes Tunisian patients (World Health Organization criteria) and 208 controls (age ≥40; fasting plasma glucose <6.1 mmol/L; without first degree family history of diabetes) has been performed. Other parameters such as diabetic nephropathy, diabetic retinopathy, cardiovascular disease, overweight/obesity and hypertension have been also collected. Genotyping was performed using TaqMan technology. RESULTS: A significant association between the rs4402960 and Type 2 diabetes (OR = 1.86, 95% CI = 1.34-2.58, P < 10(-4) ) has been found. Overweight/obese subjects bearing the T-allele have an increased risk to develop Type 2 diabetes (OR = 2.06, 95% CI = 1.40-3.03, P < 10(-4) ). Furthermore, the rs7756992 was found to be associated with the reduced risk of diabetic nephropathy in patients with diabetes (OR = 0.44, 95% CI = 0.27-0.73, P = 0.001). CONCLUSIONS: The present study confirms that the rs4402960 of IGF2BP2 gene is a strong candidate for Type 2 diabetes susceptibility and overweight/obesity risk in the Tunisian population. Interestingly, our data suggest that the rs7756992 of CDKAL1 gene have a protective effect against diabetic nephropathy.

Evidence for association of the E23K variant of KCNJ11 gene with type 2 diabetes in Tunisian population: population-based study and meta-analysis.

AIMS: Genetic association studies have reported the E23K variant of KCNJ11 gene to be associated with Type 2 diabetes. In Arab populations, only four studies have investigated the role of this variant. We aimed to replicate and validate the association between the E23K variant and Type 2 diabetes in Tunisian and Arab populations. METHODS: We have performed a case-control association study including 250 Tunisian patients with Type 2 diabetes and 267 controls. Allelic association has also been evaluated by 2 meta-analyses including all population-based studies among Tunisians and Arabs (2 and 5 populations, resp.). RESULTS: A significant association between the E23K variant and Type 2 diabetes was found (OR = 1.6, 95% CI = 1.14-2.27, and P = 0.007). Furthermore, our meta-analysis has confirmed the significant role of the E23K variant in susceptibility of Type 2 diabetes in Tunisian and Arab populations (OR = 1.29, 95% CI = 1.15-1.46, and P < 10(-3) and OR = 1.33, 95% CI = 1.13-1.56, and P = 0.001, resp.). CONCLUSION: Both case-control and meta-analyses results revealed the significant association between the E23K variant of KCNJ11 and Type 2 diabetes among Tunisians and Arabs.