[Show abstract][Hide abstract] ABSTRACT: Background:
As a result of chronic hemolysis, hyperbilirubinemia is often observed, leading to the formation of pigment cholelithiasis which could be busted by the presence of uridine diphosphoglucuronosyltransferase 1A1 defects.
Herein, we investigated the effect of glibert mutation on the occurrence of pigment cholelithiasis in Tunisian patients with beta (β) hemoglobinopathy including sickle cell anemia and β thalassemia (minor).
Subjects and methods:
Our study included 151 subjects divided in 75 SCA patients and 76 β thalassemia patients. Both groups of patients were divided into two sub-groups according to the presence or absence of cholelithiasis. The relationship between A(TA)nTAA variation of UGT1A1 gene, the serum bilirubin level and the occurrence of cholilithiasis was investigated.
Our results show a significant association between genotypes carrying variant (TA)7 and hyperbilirubinemia (p<0.05). Furthermore, we demonstrated a significant association between (TA)6/(TA)7 and (TA)7/(TA)7 genotypes with cholelithiasis among sickle cell anemia and thalassemia patients (p<0.05).
Altogether, our data provide evidence that genotypes (TA)6/(TA)7 and (TA)7/(TA)7 and (TA)7 variant present a risk factor of developing gallstone among β hemoglobinopathy Tunisian patients.
[Show abstract][Hide abstract] ABSTRACT: Runs of homozygosity (ROHs) are extended genomic regions of homozygous genotypes that record populations’ mating patterns in the past. We performed microarray genotyping on 15 individuals from a small isolated Tunisian community. We estimated the individual and population genome-wide level of homozygosity from data on ROH above 0.5 Mb in length. We found a high average number of ROH per individual (48.2). The smallest ROH category (0.5–1.49 Mb) represents 0.93% of the whole genome, while medium-size (1.5-4.99 Mb) and long-size ROH (≥5 Mb) cover 1.18% and 0.95%, respectively. We found that genealogical individual inbreeding coefficients (Fped) based on three- to four-generation pedigrees are not reliable indicators of the current proportion of genome-wide homozygosity inferred from ROH (FROH) either for 0.5 or 1.5 Mb ROH length thresholds, while identity-by-descent sharing is a function of shared coancestry. This study emphasizes the effect of reproductive isolation and a prolonged practice of consanguinity that limits the genetic heterogeneity. It also provides evidence of both recent and ancient parental relatedness contribution to the current level of genome-wide homozygosity in the studied population. These findings may be useful for evaluation of long-term effects of inbreeding on human health and for future applications of ROHs in identifying recessive susceptibility genes.
Annals of Human Genetics 09/2015; 79(6). DOI:10.1111/ahg.12131 · 2.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aims and background Hyperbilirubinemia is often observed in chronic hemolysis and results in the formation of pigment cholelithiasis that could be increased by the presence of defected enzymes involved in the bilirubin metabolism. Indeed, this is the first report that interested in the study of polymorphisms in genes encoded for enzymes involved in the bilirubin metabolism: rs 4149056 of SLCO1B1 and rs4149000 of SLCO1A2 in combination with rs8175347 and rs887829 of UGT1A1 in order to find a correlation between the polymorphisms studied and the presence of gallstones in a population of sickle cell anemia (SCA) pediatric Tunisians. Material and methods Our study involved 102 unrelated Tunisian subjects. All SCA patients are children (less than 16 years old) and were characterized by hyperbilirubinemia and 52 of them have cholelithiasis. The polymorphisms of the candidate genes were analyzed for all subjects by PCR/sequencing. Genotype and allele frequencies between cases and controls were compared using Pearson's chi-square test with a significance threshold of P < 0.05 (compare 2, version 1.02). Results The novelty of this report is that children carrying the combined genotype of the rs studied: (TA7TA7)/TT/TC/GA have a higher risk to develop gallstones (P = 0.0027, RR = 18.27 (20.0061-915.28)). Conclusion Altogether our data provide the implication of UGT1A1 and SLCO1A2 in sickle cell anemia-related cholelithiasis.
[Show abstract][Hide abstract] ABSTRACT: 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.
Mitochondrial DNA 09/2014; DOI:10.3109/19401736.2014.953136 · 1.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.).
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.).
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.
BioMed Research International 07/2014; 2014:265274. DOI:10.1155/2014/265274 · 1.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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 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 Tunisian population.
A case-control association study including 200 Type 2 diabetes Tunisian patients (WHO 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.
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 associated with the reduced risk of diabetic nephropathy in patients with diabetes (OR = 0.44, 95% CI = 0.27-0.73, p = 0.001).
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.
Journal of Diabetes 03/2014; 7(1). DOI:10.1111/1753-0407.12147 · 1.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Mitochondrial DNA 10/2013; 26(3). DOI:10.3109/19401736.2013.836508 · 1.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Differentiating malignant from benign pheochromocytoma has been challenging when based on histologic features. This is due to the definition of malignant pheochromocytoma which are defined by the presence of metastases. A PASS score was developed and according to many authors, a PASS score> =4 identified potentially malignant tumors. aim: To assess the prognostic value of PASS score in differentiating benign pheochromocytomas from malignant ones. methods: The records of 11 patients with tumors diagnosed as "pheochromocytoma" were identified from 1970 to 2010 in the files of the pathology, intern medicine and biochemistry departments of the Charles Nicolle hospital and Pasteur Institute. Receiver operating characteristics (ROC) curve analysis was performed to evaluate the diagnostic performance of PASS. The logistic model was developed using the 11 predictive variables. Its performance was evaluated by calculating the area under the ROC curve and comparing it with that of the PASS. results: In benign tumors, The PASS score was <4 in 3 cases and >=4 in 6 cases. In malignant tumors, the PASS score was >=4 in both cases. According to the ROC curve analysis, a PASS equal or superior to 4 identifies malignant pheochromocytoma with a sensitivity of 50% and a specificity of 45%. Conclusion: I think that PASS score, despite its low sensitivity, may help to reserve the more aggressive treatment and narrow follow up for potentially malignant tumors. Widespread of this called score with complete clinical data will help to validate these findings and to add other prognostic factors of value that could be a part of this scaled score such as immunohistochemical findings.
[Show abstract][Hide abstract] ABSTRACT: We report the identification of two novel polymorphisms in the PRKAG2 gene and preliminary association study between 5'-UTR and exon 1 polymorphisms with susceptibility to type 2 diabetes. No association with type 2 diabetes was identified. However, one of these newly identified polymorphisms (p.Ser20Ile) is likely associated with cardiac disease.
Diabetes research and clinical practice 12/2009; 87(2):e7-10. DOI:10.1016/j.diabres.2009.11.009 · 2.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In inflammatory diseases, classical parameters of iron status (serum iron, serum ferritin, total iron-binding capacity of transferrin and transferrin saturation) are not very reliable.
The purpose of this study is to investigate soluble transferrin receptor, its index and classical parameters of iron status [serum iron, serum ferritin, total iron-binding capacity of transferrin and transferrin saturation] during iron-deficiency anemia and combined iron deficiency and inflammatory anemia.
Our study concerned 24 patients: 18 patients with iron-deficiency anemia and 6 patients with combined iron-deficiency and inflammatory anemia. 55 healthy subjects were included as controls. Both groups underwent classical parameters of iron status [serum iron, serum ferritin, total iron-binding capacity of transferrin and transferrin saturation] and measurement of soluble transferrin receptor with its index.
In iron-deficiency anemia, total iron-binding capacity of transferrin, soluble transferrin receptor and its index were enhanced, whereas serum iron, ferritinemia and transferrin saturation were low compared to controls. Compared to patients with iron-deficiency anemia, those with combined iron-deficiency and inflammatory anemia showed higher levels of serum iron and ferritinemia. In contrast, soluble transferrin receptor and its index did not vary significantly between both groups.
Our findings show the interest of soluble transferrin receptor and its index in the detection of iron deficiency during anemia of inflammatory states.
[Show abstract][Hide abstract] ABSTRACT: We studied the relationship between spermogram parameters and biochemical elements in seminal plasma. In this way we searched an association between immunoglobulin levels in seminal plasma and spermogram parameters. The spermogram is usually performed in our laboratory for investigation of infertility. Using immunonephelometry, we measured immunoglobulin (Ig) G and A levels in the seminal plasma of 17 patients. Averages levels of IgG and IgA were 83.3 and 33.6 mg/L, respectively. IgG and IgA levels appeared to be significantly different (p = 0.001), and were significantly associated. A correlation between IgG values and coiled tails percentage was noted in patients having IgA below 20 mg/L (p < 0,001). In conclusion, the measurement of IgG and IgA levels in seminal plasma might constitute a valuable diagnosis tool for the evaluation of infertility.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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).
In the present preliminary study, the (I/D) polymorphism within the ACE gene is likely not associated with diabetic nephropathy nor with type 2 diabetes in the Tunisian studied population.
Journal of Renin-Angiotensin-Aldosterone System 04/2008; 9(1):32-6. DOI:10.3317/jraas.2008.002 · 2.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
These results suggest familial aggregation and excess maternal transmission of type 2 diabetes in the Tunisian studied population.
Postgraduate medical journal 06/2007; 83(979):348-51. DOI:10.1136/pgmj.2006.053744 · 1.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study is to evaluate the effect of fluid and diet restriction in fasting on biochemical factors of stone formation. Our study concernes 90 patients divided in three groups: healthy fasting patient (GI), healthy non fasting patient (G2) and non fasting patient with calcium lithiasis (G3). The promotors (oxalate, calcium, uric acid, phosphates) and inhibitors (citrate, magnesium) are statistically significant between G1, G2 and G3, G2. Supersaturation of urine with oxalate, uric acid and brushite are the same for (G1) and (G3) and higher than (G2). Crystalluria is more important in lithiasis subjects compared with healthy non fasting patients (58% vs 11,4%). Oxalate monohydrate (Whewellite) and uric crystal don't exist in the healthy non fasting people but reached 4% and 12% respectively in the lithiasis patient. The crystalluria profil is the same in the heathy fasting patients and calcium lithiasis patients. However healthy patients have equilibria between promotors and inhibitors of crystal formation which minimize the risk of crystalluria and subsequent stone formation.
[Show abstract][Hide abstract] ABSTRACT: The skin aging is the result of the association of seven factors; chronological factor, genetic factors, exposure to ultraviolet rays (photodamage), behaviour factors, endocrinous, catabolics and mechanics factors. The treatment combine sun protection measures, topical treatment, dermatological and surgical techniques (peelings, resurfacing laser, injections of collagen, botulic toxin...). The authors intend to study clinical and anatomy-physiology aspect of skin aging, as well as different treatments.
[Show abstract][Hide abstract] ABSTRACT: The morpho-costitutional analysis of 574 urinary lithiasis emitted by tunisean adults permitted to define an épidemiology's profile. This resemble to the épidemiology's profile of under-developed conry: Amore raised frequency of the renal lithiasis at the man than at the woman with a sec ratio of 2.4. An average age of +14 years with a peak to 4th decade in 2 sexes. The upper localitation of the calculi is founded in 94% cases. The fréquency of the relapses, the mode of expulsion and the size of calculi are différent of those published in the litérature. Probably because the time of study which last 4 years is too short, so it don't enable us to find a result like the literature. The surgery is the mode of most fréquent élimination (51%). This s dû to the présence great size calculi in our popûlation and to the récent introduction of the lithotritie in our country.
[Show abstract][Hide abstract] ABSTRACT: To report the frequency and intensity of anemia in a population of pregnant tunisian women. Our retrospective study concern 200 patients collected from january to july 1999 in a population of pregnancies. Mean age was 30.1 years and 68.5% of patients consult in the third trimester with a 33.5% rate of multiparity. The frequency of anemia is 37.5%. Anemia was ferriprive in 97.3% and hypochromic in 24% of cases. Mean ferritinemia is 4.19 ng/ml after 24 weeks of amenorrhea with a marqued decrease in case of multiparity and pregnancy evolution. Mean transferrinemia is significantly low in anemic (3.98 g/dl) versus non anemic (3.60 g/dl) patients (< 0.05). The comparison of anemia with parity, the delay between two pregnancies and term of pregnancy showed a higher risk with multiparity, short delay between two pregnancies and advanced term. The frequency of anemia in tunisian pregnant women is relatively high, prevention is based on iron supplementation and hygienodietetic advices.
[Show abstract][Hide abstract] ABSTRACT: The composition of urinary stones in children depends on socioeconomic conditions and hygiene, geographical area, and dietary
habits. We analyzed urinary stones from 120 consecutive Tunisian children (81 males, 39 females) aged 5 months to 15 years.
The stone was located in the upper urinary tract in 91 cases (76%). Stone analysis included both a morphological examination
and an infrared analysis of the nucleus and the inner and peripheral layers. The main components of bladder calculi were whewellite
(69%) and struvite (22%), whereas the main component of upper urinary tract calculi was whewellite (67%). The nucleus of bladder
stones was composed of ammonium urate (45%), struvite (28%), cystine (10%), and carbapatite (7%). The nucleus of kidney and
ureteral calculi was mainly composed of ammonium urate (38%), whewellite (24%), carbapatite (13%), or struvite (11%). Based
on stone composition, urinary tract infection was involved in the nucleation or growth of a third of calculi. Endemic urolithiasis
involving simultaneous nutritional, metabolic, and infectious factors, and defined by its nucleus composed of ammonium urate
without struvite, represented 40% of cases. Exclusive metabolic factors – including genetic diseases such as primary hyperoxaluria,
cystinuria, and hypercalciuria – were responsible for less than 25% of cases.