Microalbuminuria, Other Markers of Nephropathy and Biochemical Derangements in Type 2 Diabetes Mellitus: Relationships and Determinants

Background: Microalbuminuria is an early indicator of Diabetic nephropathy and cerebrovascular disease.Objective: To evaluate relationships between microalbuminuria and other predictors of morbidity and mortality in type 2 DM.Methods: Fifty type 2 diabetic subjects were recruited each for three groups separated by disease durations. Thirty non-diabetic subjects were recruited to control each group. Urine albumin-to-creatinine ratio (ACR) was estimated. Fasting plasma glucose (FPG), serum creatinine, urea, total cholesterol (TC), triglycerides (TG), high- and low density lipoprotein (HDL, LDL) were measured.Results: The diabetics with longest disease duration of >10 years were the oldest (65.86±1.71), had highest systolic BP (147.12±3.39mmHg) and least BMI (27.20±0.71Kg/m2); they had poorest lipid control (TC:5.54±0.26mmol/L),though with the least TG (0.97±0.09mmol/L); they also had the most severe microalbuminuria (33.63±8.03g/L) and ACR (65.85±10.38mg/gm). Patients with diabetes of 5-10 years had the poorest glycaemic control:FPG- 7.82±0.47mmol/L; HbA1c-13.09±0.74%). Significant negative correlations exist between microalbuminuria,HBA1c(r=-2.28, p=0.028) and serum creatinine(r=-2.11,p=0.042) in patients with 5-10 years disease; a positive correlation between the ACR and TC(r=1.00,p<0.01) in those with >10 years disease. In multivariate analysis, independent predictors of microalbuminuria were disease duration (OR 2.2, p< 0.001); HBA1c (OR 7.3, p=0.02); LDL/HDL ratio (OR 13.4, p< 0.001).Conclusion: The severity and progression of albuminuria are associated with longer duration of diabetes and poor glycaemic control. Significant relationships exist between ACR and HBA1c, TC, HDL-C, TG, creatinine. Disease duration, ethnicity, HBA1c, TC, TG, HDL-C and LDL/HDL ratio are independent predictors of albuminuria.Keywords: diabetes, microalbuminuria, albumin-to-creatinine ratio, dyslipidaemia, nephropathy, cardiovascular diseaseFunding: None declare

Targeted next-generation sequencing identifies novel variants in candidate genes for Parkinson’s disease in Black South African and Nigerian patients

Background: The prevalence of Parkinson’s disease (PD) is increasing in sub-Saharan Africa, but little is known about the genetics of PD in these populations. Due to their unique ancestry and diversity, sub-Saharan African populations have the potential to reveal novel insights into the pathobiology of PD. In this study, we aimed to characterise the genetic variation in known and novel PD genes in a group of Black South African and Nigerian patients. Methods: We recruited 33 Black South African and 14 Nigerian PD patients, and screened them for sequence variants in 751 genes using an Ion AmpliSeq™ Neurological Research panel. We used bcftools to filter variants and annovar software for the annotation. Rare variants were prioritised using MetaLR and MetaSVM prediction scores. The effect of a variant on ATP13A2’s protein structure was investigated by molecular modelling. Results: We identified 14,655 rare variants with a minor allele frequency ≤ 0.01, which included 2448 missense variants. Notably, no common pathogenic mutations were identified in these patients. Also, none of the known PD-associated mutations were found highlighting the need for more studies in African populations. Altogether, 54 rare variants in 42 genes were considered deleterious and were prioritized, based on MetaLR and MetaSVM scores, for follow-up studies. Protein modelling showed that the S1004R variant in ATP13A2 possibly alters the conformation of the protein. Conclusions: We identified several rare variants predicted to be deleterious in sub-Saharan Africa PD patients; however, further studies are required to determine the biological effects of these variants and their possible role in PD. Studies such as these are important to elucidate the genetic aetiology of this disorder in patients of African ancestry

Biobanking in a Challenging African Environment: Unique Experience from the SIREN Project

Africa was previously insufficiently represented in the emerging discipline of biobanking despite commendable early efforts. However, with the Human, Heredity, and Health in Africa (H3Africa) initiative, biorepository science has been bolstered, regional biobanks are springing up, and awareness about biobanks is growing on the continent. The Stroke Investigative Research and Educational Network (SIREN) project is a transnational, multicenter, hospital and community-based study involving over 3000 cases and 3000 controls recruited from 16 sites in Ghana and Nigeria. SIREN aims to explore and unravel the genetic and environmental factors that interact to produce the peculiar phenotypic and clinical characteristics of stroke as seen in people of African ancestry and facilitate the development of new diagnostics, therapeutics, and preventative strategies. The aim of this article is to describe our experience with the development of the procedure for collection, processing, storage, and shipment of biological samples (blood, serum, plasma, buffy coat, red cell concentrates, and DNA) and brain imaging across coordinating and participating sites within the SIREN Project. The SIREN network was initiated in 2014 with support and funding from the H3Africa Initiative. The SIREN Biobank currently has 3015 brain images, 92,950 blood fractions (serum, plasma, red cell concentrates, and buffy coat) accrued from 8450 recruited subjects, and quantified and aliquoted good-quality DNA extracts from 6150 study subjects. This represents an invaluable resource for future research with expanding genomic and trans-omic technologies. This will facilitate the involvement of indigenous African samples in cutting-edge stroke genomics and trans-omics research. It is, however, critical to effectively engage African stroke patients and community members who have contributed precious biological materials to the SIREN Biobank to generate appropriate evidence base for dealing with ethical, legal, and social issues of privacy, autonomy, identifiability, biorights, governance issues, and public understanding of stroke biobanking in the context of unique African culture, language, and belief systems

Serum reference intervals of micronutrients, vitamins, and interleukins among healthy adults in South-Western Nigeria

Objectives: Clinical decision making depends mostly on appropriate application of numerical pathology reports from laboratory results, interpreted by comparison with reference intervals. We determined serum reference intervals of micronutrients, vitamins, and detectable interleukins among healthy adults in South-Western Nigeria. Design and methods: This prospective study used a priori selection approach in blood-donors. They were screened for conditions that could elicit cytokine production.Serum micronutrients were assayed using Atomic Absorption Spectrophotometry; interleukins and vitamins by high Performance Liquid Chromatography. The reference intervals (RIs) were estimated at 2.5th percentile and 97.5th percentile. Results: One hundred and eighteen (118) apparently healthy subjects, aged 18–56 years; 113 (95.8%) being 18–44years, and 5 (4.2%): 45–56 years; mostly males, 13 (11.02%) females, all Africans of Yoruba ethnicity.Estimated reference limits were: Zinc: 9.49–20.54 μmol/L, Selenium: 0.50–1.11 μmol/L, Copper: 13.86–27.97 μmol/L, Iron: 14.19–32.07 μmol/L, Manganese: 6.24–16.37 nmol/L; Magnesium: 0.78–1.62 mmol/L.Vitamins: A-1.08–2.39 μmol/L; D: 59.89–164.42 μmol/L; E: 7.13–19.45 μmol/L; K: 0.16–0.42 nmol/L; B1: 74.09–201.56 nmol/L; B6: 0.12–0.29 nmol/L; B12: 155.55–407.96 pmol/L; C: 47.74–112.99 μmol/L.Detected interleukins (IL-1 to IL-18): IL-1: 0.58–1.24 ng/L, IL-2: 0.09–0.18 ng/L, IL-3: 0.39–0.89 ng/L, IL-4: 0.27–0.58 ng/L, ….to IL-18: 0.74–1.56 ng/L. Conclusions: The RI derived from this study for serum micronutrient, vitamin and interleukin concentrations are the first published for our population. They are in general agreement with those published from other geographical climes but there are differences at the lower and upper limits of the RI. The study reinforces the importance of deriving RI for the population that a clinical laboratory will serve

Targeted next-generation sequencing identifies novel variants in candidate genes for Parkinson’s disease in Black South African and Nigerian patients

CITATION: Oluwole, O. G., et al. 2020. Targeted next-generation sequencing identifies novel variants in candidate genes for Parkinson’s disease in Black South African and Nigerian patients. BMC Medical Genetics, 21:23, doi:10.1186/s12881-020-0953-1.The original publication is available at https://bmcmedgenet.biomedcentral.comBackground: The prevalence of Parkinson’s disease (PD) is increasing in sub-Saharan Africa, but little is known about the genetics of PD in these populations. Due to their unique ancestry and diversity, sub-Saharan African populations have the potential to reveal novel insights into the pathobiology of PD. In this study, we aimed to characterise the genetic variation in known and novel PD genes in a group of Black South African and Nigerian patients. Methods: We recruited 33 Black South African and 14 Nigerian PD patients, and screened them for sequence variants in 751 genes using an Ion AmpliSeq™ Neurological Research panel. We used bcftools to filter variants and annovar software for the annotation. Rare variants were prioritised using MetaLR and MetaSVM prediction scores. The effect of a variant on ATP13A2’s protein structure was investigated by molecular modelling. Results: We identified 14,655 rare variants with a minor allele frequency ≤ 0.01, which included 2448 missense variants. Notably, no common pathogenic mutations were identified in these patients. Also, none of the known PD-associated mutations were found highlighting the need for more studies in African populations. Altogether, 54 rare variants in 42 genes were considered deleterious and were prioritized, based on MetaLR and MetaSVM scores, for follow-up studies. Protein modelling showed that the S1004R variant in ATP13A2 possibly alters the conformation of the protein. Conclusions: We identified several rare variants predicted to be deleterious in sub-Saharan Africa PD patients; however, further studies are required to determine the biological effects of these variants and their possible role in PD. Studies such as these are important to elucidate the genetic aetiology of this disorder in patients of African ancestry.https://bmcmedgenet.biomedcentral.com/articles/10.1186/s12881-020-0953-1Publisher's versio

Dominant modifiable risk factors for stroke in Ghana and Nigeria (SIREN): a case-control study

Summary: Background: Sub-Saharan Africa has the highest incidence, prevalence, and fatality from stroke globally. Yet, only little information about context-specific risk factors for prioritising interventions to reduce the stroke burden in sub-Saharan Africa is available. We aimed to identify and characterise the effect of the top modifiable risk factors for stroke in sub-Saharan Africa. Methods: The Stroke Investigative Research and Educational Network (SIREN) study is a multicentre, case-control study done at 15 sites in Nigeria and Ghana. Cases were adults (aged ≥18 years) with stroke confirmed by CT or MRI. Controls were age-matched and gender-matched stroke-free adults (aged ≥18 years) recruited from the communities in catchment areas of cases. Comprehensive assessment for vascular, lifestyle, and psychosocial factors was done using standard instruments. We used conditional logistic regression to estimate odds ratios (ORs) and population-attributable risks (PARs) with 95% CIs. Findings: Between Aug 28, 2014, and June 15, 2017, we enrolled 2118 case-control pairs (1192 [56%] men) with mean ages of 59·0 years (SD 13·8) for cases and 57·8 years (13·7) for controls. 1430 (68%) had ischaemic stoke, 682 (32%) had haemorrhagic stroke, and six (<1%) had discrete ischaemic and haemorrhagic lesions. 98·2% (95% CI 97·2–99·0) of adjusted PAR of stroke was associated with 11 potentially modifiable risk factors with ORs and PARs in descending order of PAR of 19·36 (95% CI 12·11–30·93) and 90·8% (95% CI 87·9–93·7) for hypertension, 1·85 (1·44–2·38) and 35·8% (25·3–46·2) for dyslipidaemia, 1·59 (1·19–2·13) and 31·1% (13·3–48·9) for regular meat consumption, 1·48 (1·13–1·94) and 26·5% (12·9–40·2) for elevated waist-to-hip ratio, 2·58 (1·98–3·37) and 22·1% (17·8–26·4) for diabetes, 2·43 (1·81–3·26) and 18·2% (14·1–22·3) for low green leafy vegetable consumption, 1·89 (1·40–2·54) and 11·6% (6·6–16·7) for stress, 2·14 (1·34–3·43) and 5·3% (3·3–7·3) for added salt at the table, 1·65 (1·09–2·49) and 4·3% (0·6–7·9) for cardiac disease, 2·13 (1·12–4·05) and 2·4% (0·7–4·1) for physical inactivity, and 4·42 (1·75–11·16) and 2·3% (1·5–3·1) for current cigarette smoking. Ten of these factors were associated with ischaemic stroke and six with haemorrhagic stroke occurrence. Interpretation: Implementation of interventions targeting these leading risk factors at the population level should substantially curtail the burden of stroke among Africans. Funding: National Institutes of Health