Strengthening human genetics research in Africa: report of the 9th meeting of the African Society of Human Genetics in Dakar in May 2016.

The 9th meeting of the African Society of Human Genetics, in partnership with the Senegalese Cancer Research and Study Group and the Human Heredity and Health in Africa (H3Africa) Consortium, was held in Dakar, Senegal. The theme was Strengthening Human Genetics Research in Africa. The 210 delegates came from 21 African countries and from France, Switzerland, UK, UAE, Canada and the USA. The goal was to highlight genetic and genomic science across the African continent with the ultimate goal of improving the health of Africans and those across the globe, and to promote the careers of young African scientists in the field. A session on the sustainability of genomic research in Africa brought to light innovative and practical approaches to supporting research in resource-limited settings and the importance of promoting genetics in academic, research funding, governmental and private sectors. This meeting led to the formation of the Senegalese Society for Human Genetics.

Le 9ème congrès de la Société Africaine de Génétique Humaine, en partenariat avec le Groupe d'Etude et de Recherche sur le Cancer (GERC) et le Consortium H3Africa, s'est tenu à Dakar, au Sénégal. Le thème était «Renforcer la recherche en Génétique Humaine en Afrique¼. Les 210 participants sont venus de 21 pays africains et de six non africains. L'objectif était de valoriser la génétique et la génomique à travers l'Afrique avec comme but ultime d'améliorer la santé des populations, et de promouvoir les carrières des jeunes chercheurs Africains. Une session sur la pérennité de la recherche génomique a révélé des approches innovantes et pratiques supportant la recherche dans des contextes de ressources limitées et l'importance de promouvoir la formation universitaire en génétique, le financement de la recherche par les gouvernements et le privé. Ce congrès conduisit à la création de la Société Sénégalaise de Génétique Humaine.

[PPAR alpha-L162V, frequency and relationship with type 2 diabetes among black Senegalese people]. / PPARalpha-L162V: fréquence et relation avec le diabète de type 2 dans une population noire sénégalaise.

PPARs are supposed to be involved in pathogenesis of diabetes and its complications. According to some authors, L162V PPARalpha gene polymorphism would be associated to dyslipidemia susceptibility during diabetes, whereas for some authors, it rather would confer resistance to these metabolic abnormalities. The aim of this study is to search the relationship between this polymorphism and the occurrence of diabetes and its complications within a Senegalese black population constituted of 261 diabetic and 128 controls, by comparing alleles frequencies. Genomic analysis for alleles identification has been performed by the allelic discrimination technic TaqMan 5' Nuclease, after DNA extraction (Nucleon Bacc2. Amersham Int.). The results of genetic variants analysis revealed that L162V PPARalpha polymorphism would not be present among Senegalese black population, and consequently, should not be involved in diabetes onset.

[Transferrine soluble receptors' contribution to the assessment of iron status in homozygous drepanocytic anemia]. / Apport des récepteurs solubles de la transferrine dans l'évaluation du statut en fer au cours de la drépanocytose homozygote.

Sickle cell anemia does not cause martial deprivation per se, but may worsen when iron deficiency exists, notably in tropical zone where infectious diseases and malnutrition are endemic mainly during childhood. This study was aimed to assess iron deficiency prevalence among children with sickle cell disease (SCD) and to determine the best parameters for its diagnosis. In addition to classical parameters, we measured transferrine's soluble receptors which can reveal an iron deficiency, either isolated or associated to another condition since its level is not influenced by chronic anemia. Assays were carried out in 40 homozygous SCD patients, aged 3 to 18 years, having an hemoglobin level < 11 g/dL and in 30 age-paired controls assumed to be healthy and having a negative Emmel test and an hemoglobin level < 11 g/dL. The results showed hyposideremia (serum iron < 60 microg/dL) in 17.5% of the patients. Ferritinemia, transferrinemia as well as total iron fixation capacity were in the normal range for the majority of SCD patients in spite of the frequency of hyposideremia and microcytic anemia (20%). Transferrine's saturation coefficient was low in 22.5% of patients, which can be due to martial deprivation or to inflammatory status. These results confirm the limitations of usual biochemical parameters in the diagnosis of iron deficiency in homozygous drepanocytosis. Soluble receptors' levels were increased in 60% of controls; that proves that iron deficiency prevalence is high in our countries. Higher levels were found in 97.5% of patients. However, receptors' levels are increased during haemolysis, thus it is difficult to ascertain the origin of the increase, but taking into account its index value can reduces misinterpretation. In addition, considering simultaneously microcytosis, hypochromia, transferrine's soluble receptor level and its index, we can speculate that martial deficiency occurs in 20% of SCD patients, a percentage close to the 17.1% obtained by other authors using only the combination of microcytosis and hypochromia. It results from this study that associating microcytosis and hypochromia could validly assess iron deficiency during drepanocytosis.

[Prevalence of antiphospholipid antibodies in patients with sickle cell disease]. / Prévalence des anticorps antiphospholipides au cours de la drépanocytose homozygote.

Structural abnormalities in erythrocyte membrane are more and more claimed as a determinant factor in the sickle cell disease pathogenesis. This being would have been provided by a new anionic phospholipids distribution and conformation. Phosphatidyl-serine exposing and phosphatidic acid enhancing would induce specific immunoglobulins synthesis. In this study, assessment of antiphospholipid antibodies prevalence was carried out among sickle cell trait patients (n = 35) and homozygous patients (n = 59) as compared to healthy subjects (n = 39). Antiphospholipid antibodies, assayed by ELISA procedure, were significantly higher among the homozygous patients than the sickle cell trait patients ones and highlighted as compared to healthy subjects. Pathologic data were only observed among homozygous patients. These specific antibodies, associated with thrombosis and haemolysis, would have constitute a morbid link and a therapeutic target of this sickness, dominated by homodynamic troubles.

[Frequency of microalbuminuria during diabetes in Dakar, Senegal]. / Fréquence de la microalbuminurie au cours du diabète a Dakar (Senegal).

Nephropathy is one of the complications occuring during diabetes and it is diagnosed via microalbuminuria. From 1992 to 1999, five hundred and eighty seven (587) diabetic patients were recruited and distributed into two groups, A (n = 270) and B (n = 317). Microalbuminuria was determined by immunonephelemetry for group A and immunoturbidimetry for group B. The results showed respectively 15.5% and 20.19% pathological cases in the two groups (NS). Considering the distribution of patients with microalbuminuria according to the type of diabetes, there were 16.12% type 1 and 15.07% type 2 in group A against 22.60% and 18.13% in group B; no statistically significant differences were observed either in the same group or from one group to another. These frequencies might reflect the situation in the nineties; they are lower than those encountered in other populations. Nevertheless monitoring is needed through a regular schedule to prevent nephropathy.

[Defects in peroxidation of erythrocyte phospholipids in sickle cell trait]. / Lésions péroxydatives des phospholipides érythrocytaires au cours de la drépanocytose AS.

The sickle cell disease pathophysiology is provided by several events including deoxyhemoglobin S polymerization and hemorrheological troubles. Classically, such disorders have been known to concern only the homozygous SS and heterozygous SC profiles. However, troubles are more and more described since early years in the sickle cell trait patients and the pathogenesis factors are unknown. Our study focussed on phospholipids which are the basic and functional constituent elements of erythrocyte plasmic membrane. Assaying the membrane lipids extracted by Folch method and lipid standards (cholesterol, phosphatidic acid, lysophosphatidyl-choline, phosphatidyl-choline, lysophosphatidyl-ethanolamine, phosphatidyl-ethanolamine, sphingomyelin) was carried out by HPLC among 91 sickle cell trait patients as compared to 78 healthy subjects. The main abnormalities observed were an empoverishement in phosphatidyl-choline contrasting with an accumulation of membrane lysophosphatidyl-choline, lysophosphatidyl-ethanolamine, phosphatidic acid and sphingomyelin in sickle cell patients. These results suggest that sickle cell trait harmlessness is not actual. The accumulation of lysophosphatidyl-choline, by its cytolytic biomembrane perturbing properties, predispose therefore the sickled red cell to the haemolysis phenomena and allow to forecast deeper disturbances among homozygous subjects. These morbid disorders attributable to lipid peroxidation would justify an antioxidant treatment during the sickle cell disease.

[Frequency of micoalbuminuria during diabetes in Dakar (Senegal)]. / Frequence de la microalbuminurie au cours du diabète à Dakar (Sénégal).

Nephropathy is one of the complications occuring during diabetes diagnosed via microalbuminuria. From 1992 to 1999, five hundred and eighty seven (587) diabetic patients were recruited in groups A (n = 270) and B (n=317). Microalbuminuria was determined by immunonepheletry for A and immunoturbidimetry for B. The results pointed out respectively 15.5% and 20.19% pathological cases (NS). Considering the distribution of patients with microalbuminuria according to the type of diabetes there were 16.12% type 1 and 15.07% type 2 in group A against 22.60% and 18.13% in group B ; no stastically significant differences were observed either in the same group or from one group to another. These frequencies would reflect the situation in the nineties; they are lower than those encountered in other populations. Nevertheless monitoring is needed through a regular schedule to prevent nephropathy.

[Study of the anti-icteric and hepatoprotective activity of Persea gratissima Gaertner (Lauraceae) seeds ]. / Etude des activités anti-ictérique et hépatoprotectrice des amandes de Persea gratissima Gaertner (Lauraceae).

The lyophilisat of Persea gratissima Gaertner almonds was administered in various quantities to eighty four rats divided in three groups of twenty eight. in the first group (negative reference group), each animal was forcefed with 5 ml of distilled water on a daily basis, in the second group (positive reference group), the rats were forcefed with 5 ml of distilled water per day, after they were intoxicated with 0,3 ml of carbon tetrachloride under cutaneous injection, in the third group (experimental animals), each animal after it was intoxicated by the same quantity of carbon tetrachloride, was forcefed on a daily basis with 14mg/100g PV of lyophilisat of avocado almonds diluted with 5 ml of distilled water. The results showed that the lyophilisat of avocado almonds have a anti-icteric activity which is reflected in the stimulation of the liver to conjugate and eliminate bilirubin, as well as hepatoprotective activity characterised by the normalisation of the aminotransferases enzymes (ASAT, ALAT) and the healing of hepatic lesions within 10 days.

[Antidiabetic activity of Zizyphus mauritiana Lam (Rhamnaceae)]. / Etude de l'activité antidiabétique de Zizyphus mauritiana Lam (Rhamnaceae).

In traditonnal medicine, several plants were used in diabetes treatment. Among them, the aqueous extract from the leaves of Zizyphus mauritiana Lam (Rhamnaceae) was studied. The extract was administrated per os to Wistar rats made diabetics either temporarily by oral glucose tolerance test (first case) or definetely by subcutaneous injection of alloxan (second case). It was observed a striking decrease of the hyperglycemic arrow (p < 0.05) in the first case, with 300 mg/kg administrated 90 minutes before starting the test. In the second case, the results obtained with a dose of 300 mg/kg once or twice a day were identical as those with glibenclamide at 0.2 mg/kg per day. So, the antidiabetic activity of Zizyphus mauritiana Lam was experimentally born out but it has to be standardized for common use.

[Cholelithiasis and homozygote drepanocytosis in children in Dakar (Senegal)]. / Lithiase biliaire et drépanocytose homozygote en pédiatrie à Dakar (Sénégal).

BACKGROUND: Cholelithiasis is a well recognized complication of sickle-cell anemia (SCA) because of chronic hemolysis. It is usually asymptomatic but may result in acute cholecystitis or cholangitis. The aim of this study was to assess prevalence of cholelithiasis and its associated factors among Senegalese children and adolescents with SCA. PATIENTS AND METHODS: We analyzed the follow-up records and results of systematic clinical, biological and ultrasonographic examinations in 106 patients with SCA aged 11 months to 22 years (median: 10 years, 6 months), followed up in the Albert-Royer Children's Hospital (Dakar). RESULTS: Cholelithiasis was detected in 9.4% of the patients. Gender, ethnic group, geographic origin and socioeconomic conditions did not have any association with cholelithiasis frequency. The youngest patient with cholelithiasis was 7 years old, and prevalence of cholelithiasis increased with age. The mean age at the beginning of SCA follow-up was higher among patients with cholelithiasis. They were more frequently transfused and tended to present more frequent pain crises and other complications of SCA. We found no spontaneous clinical manifestations attributed to cholelithiasis. Nevertheless, provoked right upper quadrant pain was more frequently observed in patients with cholelithiasis. Fetal hemoglobin, steady-state hemoglobin, reticulocytes count, serum bilirubin, alkaline phosphatase and transaminase levels were not significantly different in these patients, compared to the others. However, those with cholelithiasis had significantly higher mean red cell volume. CONCLUSION: Prevalence of cholelithiasis appears relatively low in Senegalese patients with SCA, probably owing to the tolerance of the Senegal haplotype. Advanced age and severe chronic hemolysis are etiologic factors in evidence. We recommend systematic abdominal ultrasound at least once a year for patients older than 5 years, or when right upper quadrant pain is observed. Cholecystectomy should be performed in cases of cholelithiasis in order to prevent complications.

[Laboratory diagnosis of monoclonal gammopathies. Prospective study of 14 cases in Dakar, Senegal]. / Diagnostic au laboratoire des gammapathies monoclonales. Etude prospective de 14 cas à Dakar, Sénégal.

Monoclonal gammapathies are detected because of clinical symptoms and biological tests confirm their presence. Wishing to investigate these diseases, we carried out a series of biochemical tests on 14 patients from October 1995 to July 1996: protein, cryoglobulin, electrophoresis of proteins, proteinuria of BENCE JONES, C-reactive protein, weight measuring of immunoglobulins (Ig), immunofixation of Ig, creatinine and calcium. The results we obtained confirmed the presence of 14 cases of myeloma with: -9 IgG myelomas with 6 kappa light chains and 3 lambda light chains -4 IgA myelomas with 2 kappa light chains and 2 lambda light chains -1 IgG kappa, Ig lambda biclonal gammapathy united to a cryoglobulin of class I. We observed a predominance of the IgG over the others Ig and the kappa over the alpha light chains. The proteinuria of BENCE JONES was present among 3 patients, hypercalcemia among 4 patients and hypercreatininemia in 1 patient with chronic renal failure.