sub-Saharan Black Africans Research Articles

A genome-wide association study of plasma concentrations of warfarin enantiomers and metabolites in sub-Saharan black-African patients.

Diversity in pharmacogenomic studies is poor, especially in relation to the inclusion of black African patients. Lack of funding and difficulties in recruitment, together with the requirement for large sample sizes because of the extensive genetic diversity in Africa, are amongst the factors which have hampered pharmacogenomic studies in Africa. Warfarin is widely used in sub-Saharan Africa, but as in other populations, dosing is highly variable due to genetic and non-genetic factors. In order to identify genetic factors determining warfarin response variability, we have conducted a genome-wide association study (GWAS) of plasma concentrations of warfarin enantiomers/metabolites in sub-Saharan black-Africans. This overcomes the issue of non-adherence and may have greater sensitivity at genome-wide level, to identify pharmacokinetic gene variants than focusing on mean weekly dose, the usual end-point used in previous studies. Participants recruited at 12 outpatient sites in Uganda and South Africa on stable warfarin dose were genotyped using the Illumina Infinium H3Africa Consortium Array v2. Imputation was conducted using the 1,000 Genomes Project phase III reference panel. Warfarin/metabolite plasma concentrations were determined by high-performance liquid chromatography with tandem mass spectrometry. Multivariable linear regression was undertaken, with adjustment made for five non-genetic covariates and ten principal components of genetic ancestry. After quality control procedures, 548 participants and 17,268,054 SNPs were retained. CYP2C9*8, CYP2C9*9, CYP2C9*11, and the CYP2C cluster SNP rs12777823 passed the Bonferroni-adjusted replication significance threshold (p < 3.21E-04) for warfarin/metabolite ratios. In an exploratory GWAS analysis, 373 unique SNPs in 13 genes, including CYP2C9*8, passed the Bonferroni-adjusted genome-wide significance threshold (p < 3.846E-9), with 325 (87%, all located on chromosome 10) SNPs being associated with the S-warfarin/R-warfarin outcome (top SNP rs11188082, CYP2C19 intron variant, p = 1.55E-17). Approximately 69% of these SNPs were in linkage disequilibrium (r 2 > 0.8) with CYP2C9*8 (n = 216) and rs12777823 (n = 8). Using a pharmacokinetic approach, we have shown that variants other than CYP2C9*2 and CYP2C9*3 are more important in sub-Saharan black-Africans, mainly due to the allele frequencies. In exploratory work, we conducted the first warfarin pharmacokinetics-related GWAS in sub-Saharan Africans and identified novel SNPs that will require external replication and functional characterization before they can be considered for inclusion in warfarin dosing algorithms.

Epilepsy and skin anomalies in tuberous sclerosis complex: Report of five cases and review of the sub-Saharan African literature

Tuberous sclerosis complex (TSC) is a multi-organ disease characterized by hamartomatous involvement of several organs notably the brain, skin, eye, kidneys, heart and lungs. This rare disorder (incidence is estimated between 1/5,800 and 1/10,000 births) results from mutation of the TSC1 gene on chromosome 9q34 or from mutation of the TSC2 gene on chromosome 16q13. In 80% of cases, it is a consequence of a de novo mutation while in the remaining cases its transmission follows an autosomal dominant pattern. Epilepsy is the main neurological complication associated with TSC, with 80 to 90% of patients having epilepsy in their lifetime while skin anomalies are seen in 60 to 70% of cases. There have been few reports on TSC from sub-Saharan Africa and to the best of our knowledge none has focused specifically on neurological complications mainly epilepsy and specificities of skin abnormalities in the sub-Saharan black Africans. Five cases of TSC with characteristics skin lesions and drug resistant epilepsy are reported. Children presenting with epilepsy, especially focal epilepsy should have a careful dermatological examination. Similarly, all suspected cutaneous lesions must be evaluated with imaging study for the detection of signs of TSC. An earlier management of epilepsy may prevent cognitive impairment associated with frequent epileptic seizures.

Chronic hepatitis B virus infection and hepatocellular carcinoma in Sub-Saharan Black African children: The pre-vaccination era

With the vaccination program against hepatitis B virus (HBV) infection of new-born Black African babies not yet fully functional in sub-Saharan countries, we should remind ourselves of the frequency of chronic infection with this virus and its dire consequences, most notably the development of hepatocellular carcinoma (HCC), in the sub-Saharan Black population. Children are an early concern. Although HBV-induced HCC in sub-Saharan Black Africans occurs most often in young or middle-aged adults, the tumour also occurs in children, albeit in fewer numbers: in 1% of children less than 6 months of age, and 13% of children over one year of age [1]. The latter are, with few exceptions, aged between 5 and 15 years, and have a male/female ratio of 2 or 3:1 [1]. In common with the majority of Black African adults with HCC, most of the children with the tumour are born and live in rural areas [1-5], with the ratio of rural-born to urban-born being 4.8:1 [5]. The characteristics of HCC in children do not differ significantly from those in adults, with the possible exception of a higher incidence of an hepatic arterial bruit (66% cf 23%) [1]. The aetiology of HCC in Black African children has generally been less extensively investigated than that in adults, but those studied have shown that chronic HBV infection is the almost invariable cause of the tumour [1]. In parallel with the incidence of HCC, the presence of the virus in rural areas is appreciably greater than in urban areas: for example, Black males in the Johannesburg region have an incidence of only 1.5% and females of only 0.57% [5]. In an early study of Black African children with HCC, HBV surface antigen and antibody against the core antigen were present in the serum of all of the children, with antibody to hepatitis Be antigen being present in two-thirds [1]. These findings suggest the possibility that nearly all, or perhaps even all, Black African children with HCC are chronically infected with HBV at an early age and that the virus plays the same, if not a greater, role in causing HCC in children than it does in adults. Based on the ages of the published children with HBV-induced HCC, it seems likely that tumour formation may occur within 10 to 15 years of the initial infection. In the majority of Black children with HCC, cirrhosis is present in the non-tumorous liver. Evidence from sub-Saharan Africa and the Far East indicates that the route of acquisition of HBV in children is mainly ‘horizontal’ rather than ‘vertical’. An interval of approximately 10 years between HBV infection and the occurrence of HCC represents the usual time between exposure to the virus and the appearance of the tumour, although time spans may be as short as 6 years. The fact that the majority of Black children (and adults) with HCC live in a rural environment is attributed to the fact that the carcinogens exist in a rural to a significantly greater extent than in an urban environment. Black adults who leave the countryside to work in the cities develop the tumour at an older age (48 years) than those who remain in a rural environment (35 years) [1]. A likely co-carcinogen to HBV in the rural environment is dietary exposure to the fungal hepatocarcinogen, aflatoxin B1, and we should bear in mind that exposure to this agent remains an important cause of HCC in rural regions of subSaharan Africa, irrespective of what happens to HBV.

Hepatocellular carcinoma: epidemiology and risk factors.

Hepatocellular carcinoma is one of the major malignant tumors in the world today. The number of new cases of the tumor increases year by year, and hepatocellular carcinoma almost always runs a fulminant course and carries an especially grave prognosis. It has a low resectability rate and a high recurrence rate after surgical intervention, and responds poorly to anticancer drugs and radiotherapy. Hepatocellular carcinoma does not have a uniform geographical distribution: rather, very high incidences occur in Eastern and Southeastern Asia and in sub-Saharan Black Africans. In these regions and populations, the tumor shows a distinct shift in age distribution toward the younger ages, seen to greatest extent in sub-Saharan Black Africans. In all populations, males are more commonly affected. The most common risk factors for hepatocellular carcinoma in resource-poor populations with a high incidence of the tumor are chronic hepatitis B virus infection and dietary exposure to the fungal hepatocarcinogen aflatoxin B1. These two causative agents act either singly or synergistically. Both the viral infection and exposure to the fungus occur from early childhood, and the tumor typically presents at an early age. Chronic hepatitis C virus infection is an important cause of hepatocellular carcinoma in resource-rich countries with a low incidence of the tumor. The infection is acquired in adulthood and hepatocellular carcinoma occurs later than it does with hepatitis B virus-induced tumors. In recent years, obesity and the metabolic syndrome have increased markedly in incidence and importance as a cause of hepatocellular carcinoma in some resource-rich regions. Chronic alcohol abuse remains an important risk factor for malignant transformation of hepatocytes, frequently in association with alcohol-induced cirrhosis. Excessive iron accumulation in hereditary hemochromatosis and dietary iron overload in the Black African population and membranous obstruction of the inferior cava cause the tumor in a few countries.

Hepatitis C virus-induced hepatocellular carcinoma in sub-Saharan Africa

In sub-Saharan Africa, as in other geographical regions, the incidence and, to a lesser extent, the characteristics of hepatitis C virus (HCV)-induced hepatocellular carcinoma differ from those of the tumor caused by hepatitis B virus. HCV is a less common and less well-documented cause of hepatocellular carcinoma in the African subcontinent than it is in resource-rich regions. Perhaps surprisingly, sub-Saharan Black Africans have the highest estimated regional prevalence of chronic HCV infection globally. The infection is more common in urban than in rural dwellers. Little information is available on the age at which HCV infection is acquired in sub-Saharan Black Africans, but the incidence of chronic infection is age-related, being highest (12%) in those over the age of 40 years. No significant difference in sex distribution is evident. The documented incidence of chronic HCV infection in Black patients with hepatocellular carcinoma in the sub-continent ranges from 1.7% in the Central African Republic to 40.3% in Somalia, but varies between 10 and 20% in the majority of the countries. Patients with hepatocellular carcinoma are, on average, 20 years older than those with hepatitis B virusinduced tumors. The sex difference between the patients just fails to reach statistical significance. As with hepatocellular carcinoma in other populations, much remains to be learnt about the mechanisms involved in the pathogenesis of HCV-induced hepatocellular carcinoma in sub-Saharan Black Africans.

Hepatitis B Virus / Human Immunodeficiency Virus Co-Infection and Its Hepatocarcinogenic Potential in Sub-Saharan Black Africans

ContextSince the introduction of highly active anti-retroviral regimen for human immunodeficiency virus-1 infection, a significant increase in the incidence of hepatocellular carcinoma has been reported in patients already chronically infected with hepatitis B virus and then given this form of regimen for their retroviral infection.Evidence AcquisitionThis phenomenon was initially attributed to the far more prolonged survival of those patients who received this new regimen, which provided sufficient time, allowing hepatitis B virus-induced hepatocellular carcinoma to develop.ResultsThe current belief is that the increased incidence of hepatocellular carcinoma is because of co-infection with the two viruses, one known to be hepatocarcinogenic and the other suspected to increase the carcinogenic potential of the other. Because both hepatitis B virus and human immunodeficiency virus -1 are endemic in the Black population of sub-Saharan Africa and are transmitted in similar ways, as many as 20% of this population are co-infected with the two viruses. In this way, the already high risk of Black African patients developing hepatitis B virus-induced hepatocellular carcinoma is further increased.ConclusionsThe pathogenetic mechanism or mechanisms involved in the carcinogenic interaction between the hepatitis B virus and the human immunodeficiency virus-1 in sub-Saharan Black Africans and other populations co-infected with these viruses have yet to be determined.

Management of neural tube defects in a Sub-Saharan African country: The situation in Yaounde, Cameroon

BackgroundNeural tube defect is a serious disabling but preventable congenital malformation with an incidence of 1.99 per 1000 births in Yaounde [A.K. Njamnshi, V. d e P. Djientcheu, A. Lekoubou, M. Guemse, M.T. Obama, R. Mbu, S. Takongmo, I. Kago. Neural tube defects are rare among black Americans but not in Sub-Saharan black Africans: The case of Yaounde – Cameroon. Journal of the Neurological Sciences 2008; 270: 13–17]. The management requires highly qualified personnel and a significant social cost. The aim of this study was to evaluate the management of neural tube defect in a resource-limited developing Sub-Saharan nation like Cameroon. MethodsWe reviewed all patients with neural tube defects admitted in the neonatology unit of the Mother and Child Center (Chantal Biya Foundation Yaounde) between January 1st 2000 and December 31st 2006. ResultsSixty-nine (69) patients were enrolled. There was a male predominance (69.57%) in the sample. Myelomeningomecele represented 68.11% of cases, followed by encephalocele (27.54%) and meningocele (4.35%). Antenatal ultrasound examinations were done in 27 cases (32.8%). The prenatal diagnosis was made only in 8 cases. No medical abortion was performed in any of these cases. Medical abortion is illegal in Cameroon (except in certain specific situations) as well as other Sub-Saharan African countries. Hydrocephalus was diagnosed in 40.02% of cases. As most of the patients (62.32%) could not afford modern treatment, only 26.09% of them were operated at birth. The rest sought traditional and other forms of treatment, due to poverty or cultural beliefs. Eight patients (11.59%) died before surgery. Surgery consisted of local closure alone (40%) or local closure associated to CSF shunting (60%). The complications were wound dehiscence (13.69%), shunt infection (1.37%), meningitis (1.37%) and iatrogenic pulmonary oedema (1.37%). ConclusionNeural tube defects are the most frequent and disabling malformations in neonates in the Sub-Saharan African paediatric environment. Prenatal management and outcome at birth are limited by poverty and cultural beliefs. Prevention is possible and may be better than palliative care in developing countries.

Neural tube defects are rare among black Americans but not in sub-Saharan black Africans: The case of Yaounde — Cameroon

Neural tube defects (NTD) are complex malformations rare in black Americans and Japanese. The incidence related to births or community-based studies have not been published in Cameroon or in black sub-Saharan countries, except one study in the Nigerian middle belt [Airede KI. Neural tube defects in the middle belt of Nigeria. J Trop Pediatr 1992;38 27-30.][corrected]. To evaluate the incidence of neural tube defects in Yaounde, the birth record of the maternities was retrospectively exploited during the last ten years period (1997-2006). A total of 52,710 births were recorded in the 03 main hospitals of Yaounde. Ninety eight (98) cases of NTD with an incidence of 1.99 cases per 1000 births were registered. Spina bifida cystica (myelomeningocele, meningocele) represented 71%, followed by encephalocele (21.1%) and anencephaly (5.4%). Periconceptional folic acid was not taken by any of the mothers in our study. Abortion of affected pregnancies is illegal in Cameroon. Neural Tube Defects may not be so rare in sub-Saharan black Africans particularly in Yaounde (Cameroon). Spina bifida is the most frequent malformation. The results of this study make a case for periconceptional folic acid supplementation in our communities. The respective contributions of racial (genetic) versus environmental (or nutritional) factors will however have to be studied in order to develop a comprehensive prevention strategy.

African IQ and Mental Retardation

Rushton and Jensen (2005), in an extensive review of racial differences in intelligence test scores, assert that some part of the difference between blacks and whites in mean intelligence (IQ) scores is genetic in origin. They cite earlier reviews by Lynn (1991) and by Lynn and Vanhanen (2002), as well as several more recent studies, which are said to indicate that the mean IQ of sub-Saharan black Africans is about 70 - at the borderline of mental retardation. The present article reviews critically both the original studies and the ways in which the reviewers have described the findings of the studies.

Does a vegan diet reduce risk for Parkinson’s disease?

Three recent case-control studies conclude that diets high in animal fat or cholesterol are associated with a substantial increase in risk for ParkinsonÕs disease (PD); in contrast, fat of plant origin does not appear to increase risk. Whereas reported age-adjusted prevalence rates of PD tend to be relatively uniform throughout Europe and the Americas, sub-Saharan black Africans, rural Chinese, and Japanese, groups whose diets tend to be vegan or quasi-vegan, appear to enjoy substantially lower rates. Since current PD prevalence in African-Americans is little different from that in whites, environmental factors are likely to be responsible for the low PD risk in black Africans. In aggregate, these findings suggest that vegan diets may be notably protective with respect to PD. However, they offer no insight into whether saturated fat, compounds associated with animal fat, animal protein, or the integrated impact of the components of animal products mediates the risk associated with animal fat consumption. Caloric restriction has recently been shown to protect the central dopaminergic neurons of mice from neurotoxins, at least in part by induction of heat-shock proteins; conceivably, the protection afforded by vegan diets reflects a similar mechanism. The possibility that vegan diets could be therapeutically beneficial in PD, by slowing the loss of surviving dopaminergic neurons, thus retarding progression of the syndrome, may merit examination. Vegan diets could also be helpful to PD patients by promoting vascular health and aiding bloodÐbrain barrier transport of L-dopa.

Upregulation of lymphocyte apoptosis as a strategy for preventing and treating autoimmune disorders: a role for whole-food vegan diets, fish oil and dopamine agonists

Induced apoptosis of autoreactive T-lymphocyte precursors in the thymus is crucial for the prevention of autoimmune disorders. IGF-I and prolactin, which are lymphocyte growth factors, may have the potential to suppress apoptosis in thymocytes and thus encourage autoimmunity; conversely, dietary fish oil rich in omega-3 fats appears to upregulate apoptosis in lymphocytes. Since whole-food vegan diets may downregulate systemic IGF-I activity, it is proposed that such a diet, in conjunction with fish oil supplementation and treatment with dopamine agonists capable of suppressing prolactin secretion, may have utility for treating and preventing autoimmune disorders. This prediction is consistent with the extreme rarity of autoimmune disorders among sub-Saharan black Africans as long as they followed their traditional quasi-vegan lifestyles, and with recent ecologic studies correlating risks for IDDM and for multiple sclerosis mortality with animal product and/or saturated fat consumption. Moreover, there is evidence that vegan or quasi-vegan diets are useful in the management of rheumatoid arthritis, multiple sclerosis, and possibly SLE. The dopamine agonist bromocryptine exerts anti-inflammatory effects in rodent models of autoimmunity, and there is preliminary evidence that this drug may be clinically useful in several human autoimmune diseases; better tolerated D2-specific agonists such as cabergoline may prove to be more practical for use in therapy. The moderate clinical utility of supplemental fish oil in rheumatoid arthritis and certain other autoimmune disorders is documented. It is not unlikely that extra-thymic anti-inflammatory effects contribute importantly to the clinical utility of vegan diets, bromocryptine, and fish oil in autoimmunity. The favorable impact of low latitude or high altitude on autoimmune risk may be mediated by superior vitamin D status, which is associated with decreased secretion of parathyroid hormone; there are theoretical grounds for suspecting that parathyroid hormone may inhibit apoptosis in thymocytes. Androgens appear to up-regulate thymocyte apoptosis, may be largely responsible for the relative protection from autoimmunity enjoyed by men, and merit further evaluation for the management of autoimmunity in women. It will probably prove more practical to prevent autoimmune disorders than to reverse them once established; a whole-food vegan diet, coupled with fish oil and vitamin D supplemention, may represent a practical strategy for achieving this prevention, while concurrently lowering risk for many other life-threatening ‘Western’ diseases.