ABSTRACT
OBJECTIVE: Worldwide, the highest frequencies of APOL1-associated kidney variants are found in indigenous West Africans among whom small vessel disease (SVD) ischemic stroke is the most common stroke phenotype. The objective of this study was to investigate the association and effect sizes of 23 selected SNPs in 14 genes of relevance, including the APOL1 G1 variants, with the occurrence of SVD ischemic stroke among indigenous West African participants in the Stroke Investigative Research and Education Network (SIREN) Study. MATERIALS AND METHODS: Cases were consecutively recruited consenting adults (aged 18 years or older) with neuroimaging-confirmed first clinical stroke. Stroke-free controls were ascertained using a locally validated version of the Questionnaire for Verifying Stroke-Free Status (QVSFS). Logistic regression models adjusting for known vascular risk factors were fitted to assess the associations of the 23 SNPs in rigorously phenotyped cases (N = 154) of SVD ischemic stroke and stroke-free (N = 483) controls. RESULTS: Apolipoprotein L1 (APOL1) rs73885319 (OR = 1.52; CI: 1.09-2.13, P-value = .013), rs2383207 in CDKN2A/CDKN2B (OR = 3.08; CI: 1.15-8.26, P -value = .026) and rs2107595 (OR = 1.70; CI: 1.12-2.60, P-value = .014) and rs28688791 (OR = 1.52; CI: 1.03-2.26, P-value = .036) in HDAC9 gene were associated with SVD stroke at 0.05 significance level. Polymorphisms in other genes did not show significant associations. CONCLUSION: This is the first report of a specific association of APOL1 with a stroke subtype. Further research is needed to confirm these initial findings and deepen understanding of the genetics of stroke in people of African ancestry with possible implications for other ancestries as all humans originated from Africa.
Subject(s)
Apolipoprotein L1/genetics , Genetic Predisposition to Disease/genetics , Stroke/genetics , Adult , Aged , Black People/genetics , Brain Ischemia/genetics , Cyclin-Dependent Kinase Inhibitor p15/genetics , Cyclin-Dependent Kinase Inhibitor p16 , Cyclin-Dependent Kinase Inhibitor p18/genetics , Female , Genotype , Histone Deacetylases/genetics , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide , Repressor Proteins/genetics , Risk FactorsABSTRACT
BACKGROUND: Most (86%) of the global stroke mortality are from low- and middle-income countries (LMIC) including African countries which have the highest prevalence of the sickle cell trait (Hb AS). The effects of this trait on stroke occurrence and outcome are poorly understood. We aimed to investigate the effects of the sickle cell trait on the 30-day stroke mortality in Nigerian-Africans. METHOD: This was a prospective study of 35 stroke patients with sickle cell trait (Haemoglobin AS) and 35 age and sex-matched controls without haemoglobinopathy (Haemoglobin AA). Haemoglobin electrophoresis was performed for all before recruitment and they all had neuroimaging done. Patients with haemoglobin AS were used as cases and those with haemoglobin AA as controls. The National Institute of Health Stroke Scale (NIHSS) was used to assess the severity of stroke at presentation and the Modified Rankin Scale for 30-day stroke outcome. RESULT: There was no significant difference in the baseline stroke severity between the two groups (p = 0.21). Univariate analysis of the factors predicting the 30-day stroke outcome revealed that NIHSS score > 20 (p < 0.001), haemorrhagic stroke (p = 0.01) and the presence of Hb AS (p < 0.001) were significantly associated with 30-day mortality. Haemorrhagic stroke type was strongly associated with HbAS (OR = 2.9, 95% CI = 1.10-7.99, p-value = 0.02). With multiple logistic regression model, the presence of Hb AS (p = 0.01) and NIHSS score > 20 (p = 0.05) emerged as independent risk factors for 30-day mortality. The cases had worse stroke outcome at 30 days. CONCLUSION: Stroke had1 a worse 30-day mortality and outcome in patients with sickle cell trait (HbAS) than in patients with normal adult haemoglobin (HbAA).
