Stroke prevalence amongst sickle cell disease patients in Nigeria: a multi-centre study

Background

Stroke is a life-changing, debilitating complication of sickle cell disease (SCD). Previous studies had recorded high stroke prevalence amongst this group of patients. Nigeria has a large population of people affected by this condition and this study aims to assess the stroke prevalence in this large population.

Methodology

Stroke prevalence data from 14 physicians working in 11 tertiary health centres across the country was collated by doctors using the sickle cell registers and patient case notes. This data was then collated and used to obtain the overall stroke prevalence in adult and children.

Results

The stroke prevalence in sickle cell disease patients in Nigeria was observed to be 12.4 per 1000 patients. Prevalence in the adult patients was 17.7 per 1000 patients and 7.4 per 1000 patients in children. Twenty three percent of the affected patients had more than stroke episode.

Conclusion

The stroke prevalence in Nigeria is lower than previously recorded rates and further studies will be required to investigate other factors which may play a role.     

N-acetyltransferase 2 (NAT2) gene polymorphisms in Parkinson's disease

Background  

Parkinson's disease (PD) is a movement disorder caused by the degeneration of dopaminergic neurons in the substantia nigra of the midbrain. The molecular basis of this neural death is unknown, but genetic predisposition and environmental factors may cause the disease. Sequence variations in N-acetyltransferase 2 (NAT2) gene leading to slow acetylation process have been associated with PD, but results are contradictory.     

Vitamin D Deficiency in Adult Sickle Cell Patients

Introduction

Vitamin D levels in adult black Americans with sickle cell disease (SCD) are comparatively lower than those found in the general population of black Americans. The objectives of this study were to examine the prevalence of Vitamin D deficiency (VDD) in adults with various subtypes of sickle cell disease and identify risk factors for vitamin D deficiency.

Variants of the <Emphasis Type="Italic">Matrix Metalloproteinase-2</Emphasis> but not the <Emphasis Type="Italic">Matrix Metalloproteinase-9</Emphasis> genes significantly influence functional outcome after stroke

Background  

Multiple lines of evidence suggest that genetic factors contribute to stroke recovery. The matrix metalloproteinases -2 (MMP-2) and -9 (MMP-9) are modulators of extracellular matrix components, with important regulatory functions in the Central Nervous System (CNS). Shortly after stroke, MMP-2 and MMP-9 have mainly damaging effects for brain tissue. However, MMPs also have a beneficial activity in angiogenesis and neurovascular remodelling during the delayed neuroinflammatory response phase, thus possibly contributing to stroke functional recovery.     

Cathepsin D SNP associated with increased risk of variant Creutzfeldt-Jakob disease

Background  

Variant Creutzfeldt-Jakob disease (vCJD) originally resulted from the consumption of foodstuffs contaminated by bovine spongiform encephalopathy (BSE) material, with 163 confirmed cases in the UK to date. Many thousands are likely to have been exposed to dietary infection and so it is important (for surveillance, epidemic modelling, public health and understanding pathogenesis) to identify genetic factors that may affect individual susceptibility to infection. This study looked at a polymorphism in the cathepsin D gene (refSNP ID: rs17571) previously examined in Alzheimer's disease (AD).     

Sickle cell anemia: Intracranial stenosis and silent cerebral infarcts in children with low risk of stroke

Purpose:Children with sickle cell anemia (SCA), who have mean blood flow velocities <170 cm/s in the terminal internal carotid (tICA) or middle cerebral (MCA) arteries on transcranial Doppler ultrasonography (TCD), are considered to be at low risk of stroke. The prevalence of intracranial stenosis, which raises the risk of stroke, is not known in these children. Here, we estimated the prevalence of stenosis and explored its association with silent cerebral infarcts determined based on Magnetic Resonance (MR) scans.Patients/methodsWe studied prospectively a cohort of 67 children with SCA without prior clinically overt stroke or TIA (median age 8.8 years; range limits 2.3–13.1 years; 33 females) and with TCD mean velocity <170 cm/s. They underwent MR imaging of the brain and MR angiography of intracranial arteries.ResultsIn 7 children (10.5%, 95% CI: 4.9–20.3%) we found 10 stenoses, including 4 with isolated left tICA stenosis and 3 with multiple stenoses. We found silent infarcts in 26 children (37.7%, 95% CI: 27.2–49.5%). The median number of infarcts in an affected child was 2 (range limits: 1–9), median volume of infarcts was 171 mm³ (range limits: 7–1060 mm³), and median infarct volume in relation to total brain volume was 0.020% (range limits: 0.001–0.101%). The number and volume of infarcts were significantly higher in children with arterial stenosis (both p = 0.023).ConclusionsThe prevalence of intracranial arterial stenosis in children with SCA classified as at low risk of stroke by TCD mean velocity <170 cm/s is high. Children with stenosis are at higher risk of brain parenchymal injury as they have more silent cerebral infarcts.     

Novel quantitative trait locus is mapped to chromosome 12p11 for left ventricular mass in Dominican families: the Family Study of Stroke Risk and Carotid Atherosclerosis

Background  

Left ventricular mass (LVM) is an important risk factor for stroke and vascular disease. The genetic basis of LVM is unclear although a high heritability has been suggested. We sought to map quantitative trait loci (QTL) for LVM using large Dominican families.     

The Siblings With Ischemic Stroke Study (SWISS) Protocol

Background  

Family history and twins studies suggest an inherited component to ischemic stroke risk. Candidate gene association studies have been performed but have limited capacity to identify novel risk factor genes. The Siblings With Ischemic Stroke Study (SWISS) aims to conduct a genome-wide scan in sibling pairs concordant or discordant for ischemic stroke to identify novel genetic risk factors through linkage analysis.     

Oxidative profile of sickle cell patients in a Cameroonian urban hospital

Background

Sickle cell disease (SCD) is a class of hemoglobinopathy resulting from a single mutation in the ß-globin chain inducing the substitution of valine for glutamic acid at the sixth amino acid position which leads to the production of abnormal haemoglobin (haemoglobin S [HbS]). Studies demonstrated the implication of oxidative stress in the development of the sickle cell disease.

Methods

The study aim was to determine the level of oxidative stress markers in a group of sickle cell homozygous patients (SS) in the Yaounde Central Hospital above 15 years of age. Hemolysates obtained from patients were used to investigate some oxidative stress markers including malondialdehyde (MDA), nitric oxide (NO), catalase (CAT), superoxide dismutase (SOD), peroxidase, total antioxidant capacity (TAC) and total protein concentration.

Results

Eighty four individuals, 42 males and 42 females participated (50 % each) with an age range of 15 to 55 years. The levels of markers were significantly higher in the healthy AA group than sickle (SS) (p?<?0.05), with the exception of MDA which was significantly high in sickle cell (SS) patients than healthy (p?=?0.037). With respect to the gender, both healthy and SS females showed a greater Total anti-oxidant capacity (65 μM) compared to the males (55 μM).

Conclusion

The increase in the oxidative stress level especially MDA in sickle cell homozygous patients compared to healthy AA individuals confirms that oxidative stress is involved in the pathogenesis of the sickle cell disease.

     

Schooling of the child and teenager suffering from sickle-cell disease in 2004, Brazzaville, Congo

A case-control transversal study has been carried out in March 2004 in the paediatric unit of the Brazzaville teaching Hospital to assess the impact of the sickle cell disease on school-age children. School-age children and teenagers of both sex were distributed in 228 homozygote sickle cell children (group I) aged of 5 years old and 8 months old to 21 and 245 children recruited in state schools aged of 5 years old and 6 months to 19 years old. In the group I, 78 children suffering from sickle cell disease are ahead in their school achievement, 59 have a normal education and 91 meet some difficulties with no significant difference; in the group II, 122 children are ahead in their school achievement, 81 have a normal education and 42 meet difficulties (p < 0,001). The average of children having school difficulties was 2,4 +/- 1,5 years in the group I with extremes ranging from 1 to 3 years. By comparing both groups in primary school, no difference was to be found in children doing well at school and children having a normal education: 54 children of the group II are reported being ahead in their school achievement (39, 7%) and 81 children in the group II (55, 1%); normal education for 38 children of the group 1 (28%) and 58 children in the group II (39, 5%). On the other hand, 44 children are having school difficulties in the group I (32, 3%) against 8 children in the group II (5, 4%) (p < 0,001). As a matter of form we have observed that ahead schooling is to be found in 24 sickle cell children at HbF < 10% (41, 4%) and 54 sickle cell children at HbF < 10% (34, 2%) (p < 0,05); normal education in 14 children with sickle cell disease at HbF > 10% (24, 1%) and 45 children with sickle cell disease at HbF < 10% (25, 9%) and school difficulties in 20 children with sickle cell disease at HbF > 10% (34, 5%) and 71 children with sickle cell disease at HbF < 10% (39, 9%).     

Nitric oxide synthase 2A (NOS2A) polymorphisms are not associated with invasive pneumococcal disease

Background  

Streptococcus pneumoniae (pneumococcus) is responsible for over one million deaths per year, with young children, the elderly and immunocompromised individuals being most at risk. Approximately half of East African children have been reported to be asymptomatic carriers of pneumococcus with invasive infection occurring after the disruption of the respiratory membrane which is believed to be caused by the host immune response. Racial incidence of invasive pneumococcal disease (IPD) is higher in certain populations even after adjusting for environmental factors suggesting a genetic component to disease susceptibility. The nitric oxide synthase 2A (NOS2A) gene is responsible for the production of nitric oxide under pathological conditions including host defence against bacterial infection. Nitric oxide is a modulator of apoptotic and inflammatory cascades and endothelial permeability. We hypothesised that genetic variants within this gene may predispose to disease risk and survival.     

Enhanced genetic maps from family-based disease studies: population-specific comparisons

Background  

Accurate genetic maps are required for successful and efficient linkage mapping of disease genes. However, most available genome-wide genetic maps were built using only small collections of pedigrees, and therefore have large sampling errors. A large set of genetic studies genotyped by the NHLBI Mammalian Genotyping Service (MGS) provide appropriate data for generating more accurate maps.     

<Emphasis Type="Italic">Hunter disease eClinic:</Emphasis>interactive,computer-assisted,problem-based approach to independent learning about a rare genetic disease

Background  

Computer-based teaching (CBT) is a well-known educational device, but it has never been applied systematically to the teaching of a complex, rare, genetic disease, such as Hunter disease (MPS II).     

Lack of MEF2A Δ7aa mutation in Irish families with early onset ischaemic heart disease, a family based study

Background  

Ischaemic heart disease (IHD) is a complex disease due to the combination of environmental and genetic factors. Mutations in the MEF2A gene have recently been reported in patients with IHD. In particular, a 21 base pair deletion (Δ7aa) in the MEF2A gene was identified in a family with an autosomal dominant pattern of inheritance of IHD. We investigated this region of the MEF2A gene using an Irish family-based study, where affected individuals had early-onset IHD.     

A novel study of Copy Number Variations in Hirschsprung disease using the Multiple Ligation-dependent Probe Amplification (MLPA) technique

Background  

Hirschsprung disease (HSCR) is a congenital malformation of the hindgut produced by a disruption in neural crest cell migration during embryonic development. HSCR has a complex genetic etiology and mutations in several genes, mainly the RET proto-oncogene, have been related to the disease. There is a clear predominance of missense/nonsense mutations in these genes whereas copy number variations (CNVs) have been seldom described, probably due to the limitations of conventional techniques usually employed for mutational analysis.     

The intron 4c allele of the NOS3 gene is associated with ischemic stroke in African Americans

Background  

Ischemic stroke is the most common cause of disability in North America and in addition to the generally accepted risk factors, there is increasing evidence for the potential pathophysiological role of genes. One of these genes, the endothelial nitric oxide synthase gene (NOS3) has been reported as a genetic risk factor for ischemic stroke. To independently confirm and extend the results of these previous reports, we investigated this gene as a risk factor for stroke in an ethnically diverse study population.     

Genome-wide association reveals three SNPs associated with sporadic amyotrophic lateral sclerosis through a two-locus analysis

Background  

Amyotrophic lateral sclerosis (ALS) is a fatal, degenerative neuromuscular disease characterized by a progressive loss of voluntary motor activity. About 95% of ALS patients are in "sporadic form"-meaning their disease is not associated with a family history of the disease. To date, the genetic factors of the sporadic form of ALS are poorly understood.     

SNP-SNP interactions dominate the genetic architecture of candidate genes associated with left ventricular mass in african-americans of the GENOA study

Background  

Left ventricular mass (LVM) is a strong, independent predictor of heart disease incidence and mortality. LVM is a complex, quantitative trait with genetic and environmental risk factors. This research characterizes the genetic architecture of LVM in an African-American population by examining the main and interactive effects of individual candidate gene single nucleotide polymorphisms (SNPs) and conventional risk factors for increased LVM.     

The rs1990760 polymorphism within the IFIH1 locus is not associated with Graves' disease, Hashimoto's thyroiditis and Addison's disease

Background  

Three genes have been confirmed as major joint susceptibility genes for endocrine autoimmune disease:human leukocyte antigen class II, cytotoxic T-lymphocyte antigen 4 and protein tyrosine phosphatase non-receptor type 22. Recent studies showed that a genetic variation within the interferon induced helicase domain 1 (IFIH1) locus (rs1990760 polymorphism) is an additional risk factor in type 1 diabetes and Graves' disease (GD).