Secondhand smoke exposure is independently associated with stroke among non-smoking adults in West Africa.

BACKGROUND: Stroke is a leading cause of disability and mortality worldwide, but little is known about the contribution of secondhand smoke exposure (SHSE) to stroke epidemiology among indigenous Africans. OBJECTIVE: To evaluate the association of SHSE with stroke among indigenous Africans. METHODS: We analyzed the relationship of SHSE with stroke among 2990 case-control pairs of adults who had never smoked (identified in the SIREN study) using conditional logistic regression at a two-sided P < 0.05. RESULTS: Multivariable-adjusted odds ratio and 95% confidence interval; 1.25 (1.04, 1.50; P = 0.02) revealed SHSE was positively associated with stroke independent of stroke subtypes. CONCLUSION: Culturally relevant primary prevention strategies targeted at SHSE might be promising in preventing stroke among Africans.

Serum Interleukin-6 and Weight Loss in Antiretroviral-naïve and Antiretroviral-treated Patients with HIV/AIDS: Relationships and Predictors.

BACKGROUND: Cachexia is usually associated with elevated serum interleukin-6 (IL.6) as it stimulates the breakdown of muscle proteins and promotes wasting. OBJECTIVE: A case-control study to evaluate the relationship between weight loss, facial fat loss, and IL-6 in antiretroviral-naïve and treated participants living with HIV/AIDS. METHODS: IL-6 was assayed by High performance liquid chromatography (HPLC) in 97 in consecutive newly diagnosed antiretroviral-naive (ART-naïve) people living with HIV/AIDS (age ≥18 years); and 118 consecutive, age-matched participants currently on Highly Active Antiretroviral Therapy (HAART), using age as a criterion. In the treated group, 78 (66.7%) subjects were on zidovudine, lamivudine with nevirapine (Z+L+N); 27(23.1%) on tenofovir, lamivudine with emtricitabine (T+L+E); 5(4.3%) on zidovudine, lamivudine with emtricitabine (Z+L+E); 4(3.4%) on zidovudine, lamivudine with tenofovir (Z+L+T); 2(1.7%) on lamivudine, tenofovir with nevirapine (L+T+N); 1(0.9%) on tenofovir, zidovudine, emtricitabine (Z+T+E). RESULTS: A total of 215 participants: 97 ART-naive and 118 HAART-treated, age-matched subjects (40.3±9.6 versus 42.7±10.20years, p=0.08). The mean IL-6 was significantly higher in naïve than treated (0.69±0.04 versus 0.66±0.04 pg/ml, p =0.002). In all, 73 subjects experienced weight loss, 56(76.7%) naive, 17(23.3%) treated, p <0.0001, with significantly higher IL-6 in those with weight loss (0.69±0.05 versus 0.67±0.05pg/ml, p= 0.047). Fifty-eight (27.0%) subjects experienced facial fat loss, 49 (84.5%) naïve, and 9 (15.5%) treated, p <0.0001, with significantly higher IL-6 in those with facial fat loss (0.7 ± 0.05 versus 0.67±0.05pg/ml, p= 0.0001). Negative correlation exists between IL-6 and CD4+ count (r=-0.141, p=0.041). In logistic regression, independent predictors of weight loss include: IL-6 (Adjusted Odds Ratio, aOR 1.3, 95%CI 0·1-2·6, p=0.047); HIV duration (aOR 11.6, p <0.0001); AIDS-defining illness (aOR 3.5, p <0.0001); CD4+ count (aOR 3.2, p=0.004); HAART status (aOR 2.7, p<0.0001). CONCLUSION: HIV infection is associated with elevation of serum interleukin-6, which likely contributes to weight and facial fat loss among the treatment-naïve participants; while HAART is associated with suppressed IL-6 levels, thereby ameliorating weight and facial fat loss. Inverse relationship exists between serum IL-6 and CD4+ count; serum IL-6 could differentiate between mild- to moderate and severe immunosuppressive states.

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.

Microalbuminuria, Other Markers of Nephropathy and Biochemical Derangementsin 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. FUNDING: None declared.