Imen Arfa

Consanguinity, endogamy, and genetic disorders in Tunisia

Consanguinity refers to marriages between individuals who share at least one common ancestor. In clinical genetics, a consanguineous marriage is defined as a union between two individuals who are related as second cousins or closer, with the inbreeding coefficient (F) equal or higher than 0.0156 (Bittles2001). However, reports on consanguinity rates may sometimes include marriages between third cousins or more distantly related individuals (Hamamy2011). It is estimate that more than 690 million people in the world are consan- guineous (Bittles and Black 2010 ). Middle East, Northern Africa, and South Asia are regions that have historically and culturally had a high rate of consanguineous unions (Al- Awadi et al. 1985; Al-Gazali et al.1997; Jaber et al.1997;Bittles et al.2002; Bener and Alali2006). Recent studieshave shown that 20 % to 50 % of marriages in Arab countries are between relatives (Tadmouri et al. 2009;Bittles2011; Hamamy et al.2011). The rate was 68 % inEgypt (Mokhtar and Abdel-Fattah2001), 51-58 % in Jordan

Lack of association between the angiotensin-converting enzyme gene (I/D) polymorphism and diabetic nephropathy in Tunisian type 2 diabetic patients

Objective. The aim of the present study was to investigate whether the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism is associated with diabetic nephropathy and type 2 diabetes in the Tunisian population. Design. A case-control study was conducted among 141 unrelated type 2 diabetic patients with (90 patients) or without nephropathy (51 patients) and 103 non-diabetic controls with normal fasting blood glucose. Genotyping was performed using a nested polymerase chain reaction amplification in order to identify correctly heterozygous individuals. Results. The distribution of DD, ID and II genotypes did not significantly differ between type 2 diabetic patients with or without nephropathy (DD: 44%; ID: 46%; II: 10% vs. DD: 41%; ID: 47 %; II: 12%, respectively).There was also no significant statistical difference between the genotype distribution and allele frequencies of the (I/D) polymorphism in all type 2 diabetic subjects compared to non-diabetic controls with normal fasting blood glucose (DD: 43%; ID: 46%; II: 11% vs. DD: 37%; ID: 48% ;II: 15%, respectively). Conclusions. In the present preliminary study, the (I/D) polymorphis within the ACE gene is likely not associated with diabetic nephropathy nor with type 2 diabetes in the Tunisian studied population.

Familial aggregation and excess maternal transmission of type 2 diabetes in Tunisia

Aim: To evaluate the degree of familial aggregation of type 2 diabetes mellitus in Tunisia and to investigate transmission patterns of the disease and their relationships with patients’ clinical profiles. Methods: Family history of diabetes and clinical data were collected for 132 unrelated type 2 diabetic Tunisian patients. Diabetes status was recorded for first degree relatives (parents, siblings) and second degree relatives (aunts and uncles from both maternal and paternal sides). Information about family history of diabetes was gathered for a total of 1767 individuals. Results: Familial aggregation of type 2 diabetes was prominent and more important among first degree relatives than among second degree relatives (p = 0.01). Among studied subjects, 70% reported at least one relative with diabetes and 34% had at least one parent with diabetes. Diabetes was more frequent among mothers than fathers of probands (p = 0.03). This maternal effect extends to second degree relatives as diabetes was more common among maternal than paternal aunts and uncles (p = 0.01). There is no significant difference in clinical and metabolic profiles between patients according to transmission patterns of the disease. Conclusion: These results suggest familial aggregation and excess maternal transmission of type 2 diabetes in the Tunisian studied population.

Contribution of CDKAL1 rs7756992 and IGF2BP2 rs4402960 polymorphisms in type 2 diabetes, diabetic complications, obesity risk and hypertension in the Tunisian population 在突尼斯人群中，CDKAL1 rs7756992与IGF2BP2 rs4402960的多态性对2型糖尿病、糖尿病并发症、肥胖风险以及高血压的影响

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.

Type 2 diabetes in Mauritania: Prevalence of the undiagnosed diabetes, influence of family history and maternal effect

AIM We estimated the prevalence of undiagnosed diabetes, analyzed the influence of family history on the occurrence of T2D and evaluated its aggregation pattern in the Mauritanian population. METHODS The prevalence of unknown diabetes was obtained using data compiled from 1278 Mauritanian adults applying a questionnaire and fasting serum glucose tests. Detailed family history of diabetes and clinical characteristics were gathered from 421 T2D patients. RESULTS The prevalence of undiagnosed diabetes was 4.7 ± 1.2% in the studied population (3.1% in men and 6.4% in women). 27% of T2D patients reported at least one relative with diabetes. Association between family history and diabetes was higher among first degree compared to second degree relatives (p=0.003). We observed more probands with an affected mother than those who have a father with diabetes (p = 0.002), suggesting a preferential maternal effect which did not extend to second degree relatives. CONCLUSIONS These results show that the prevalence of diabetes in the Mauritanian population could be higher than currently thought. Family history screening may be used in the management of this condition in Mauritania.

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

Abstract 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.

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.

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

Abstract 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.

Contribution ofCDKAL1rs7756992 andIGF2BP2rs4402960 polymorphisms in type 2 diabetes, diabetic complications, obesity risk and hypertension in the Tunisian population 在突尼斯人群中，CDKAL1rs7756992与IGF2BP2rs4402960的多态性对2型糖尿病、糖尿病并发症、肥胖风险以及高血压的影响: Polymorphism complications in T2DM Tunisians

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.

Clinical and genetic investigation of pediatric cases of Wolff-Parkinson-White syndrome in Tunisian families

BACKGROUND Wolff-Parkinson-White (WPW) syndrome is an autosomal-dominant heart disease characterized by an accessory pathway that arises from an aberrant conduction from the atria to the ventricles. Several mutations within the PRKAG2 gene were shown to be responsible for WPW. This gene encodes the γ2 regulatory subunit of adenosine monophosphate (AMP)-activated protein kinase, which functions as a metabolic sensor in cells, responding to cellular energy demands. METHODS This first study of WPW in a North African population comprises the clinical and genetic investigation of 3 Tunisian families, including 11 affected members. The involvement of the PRKAG2 and NKX2-5 genes was investigated. RESULTS Mutation screening showed that with the exception of two already reported single-nucleotide polymorphisms, no mutations were detected within the coding region of PRKAG2 or in the NKX2-5 gene. CONCLUSIONS This study provides further evidence of the genetic heterogeneity of WPW.