Interleukin-6 (\u3cem\u3eIL-6\u3c/em\u3e) rs1800796 and Cyclin Dependent Kinase Inhibitor (\u3cem\u3eCDKN2A/CDKN2B\u3c/em\u3e) rs2383207 Are Associated with Ischemic Stroke in Indigenous West African Men

Background—Inherited genetic variations offer a possible explanation for the observed peculiarities of stroke in sub – Saharan African populations. Interleukin–6 polymorphisms have been previously associated with ischemic stroke in some non-African populations. Aim—Herein we investigated, for the first time, the association of genetic polymorphisms of IL-6 and CDKN2A- CDKN2B and other genes with ischemic stroke among indigenous West African participants in the Stroke Investigative Research and Education Network (SIREN) Study. Methods—Twenty-three previously identified single nucleotide polymorphisms (SNPs) in 14 genes of relevance to the neurobiology of ischemic stroke were investigated. Logistic regression models adjusting for known cardiovascular disease risk factors were constructed to assess the associations of the 24 SNPs in rigorously phenotyped cases (N=429) of ischemic stroke (Men = 198; Women = 231) and stroke– free (N=483) controls (Men = 236; Women = 247). Results—Interleukin-6 (IL6) rs1800796 (C minor allele; frequency: West Africans = 8.6%) was significantly associated with ischemic stroke in men (OR = 2.006, 95% CI = [1.065, 3.777], p = 0.031) with hypertension in the model but not in women. In addition, rs2383207 in CDKN2A/CDKN2B (minor allele A with frequency: West Africans = 1.7%) was also associated with ischemic stroke in men (OR = 2.550, 95% CI = [1.027, 6.331], p = 0.044) with primary covariates in the model, but not in women. Polymorphisms in other genes did not show significant association with ischemic stroke. Conclusion—Polymorphisms rs1800796 in IL6 gene and rs2383207 in CDKN2A/CDKN2B gene have significant associations with ischemic stroke in indigenous West African men. CDKN2A/CDKN2B SNP rs2383207 is independently associated with ischemic stroke in indigenous West African men. Further research should focus on the contributions of inflammatory genes and other genetic polymorphisms, as well as the influence of sex on the neurobiology of stroke in people of African ancestry

Additional file 1: of Phone-based Intervention under Nurse Guidance after Stroke (PINGS): study protocol for a randomized controlled trial

SPIRIT checklist. (DOC 121 kb

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