Dataset Information

APOL1, CDKN2A/CDKN2B, and HDAC9 polymorphisms and small vessel ischemic stroke.

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.

SUBMITTER: Akinyemi R

PROVIDER: S-EPMC5716854 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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APOL1, CDKN2A/CDKN2B, and HDAC9 polymorphisms and small vessel ischemic stroke.

Akinyemi R R Tiwari H K HK Arnett D K DK Ovbiagele B B Irvin M R MR Wahab K K Sarfo F F Srinivasasainagendra V V Adeoye A A Perry R T RT Akpalu A A Jenkins C C Arulogun O O Gebregziabher M M Owolabi L L Obiako R R Sanya E E Komolafe M M Fawale M M Adebayo P P Osaigbovo G G Sunmonu T T Olowoyo P P Chukwuonye I I Obiabo Y Y Onoja A A Akinyemi J J Ogbole G G Melikam S S Saulson R R Owolabi M M

Acta neurologica Scandinavica 20171003 1

<h4>Objective</h4>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 ...[more]

PMID: 28975602

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Project description:ObjectivesWe aim to investigate whether cerebral small vessel disease (cSVD) imaging markers correlate with deep medullary vein (DMV) damage in small vessel occlusion acute ischemic stroke (SVO-AIS) patients.MethodsThe DMV was divided into six segments according to the regional anatomy. The total DMV score (0-18) was calculated based on segmental continuity and visibility. The damage of DMV was grouped according to the quartiles of the total DMV score. Neuroimaging biomarkers of cSVD including white matter hyperintensity (WMH), cerebral microbleed (CMB), perivascular space (PVS), and lacune were identified. The cSVD score were further analyzed.ResultsWe included 229 SVO-AIS patients, the mean age was 63.7 ± 23.1 years, the median NIHSS score was 3 (IQR, 2-6). In the severe DMV burden group (the 4th quartile), the NIHSS score grade (6 (3-9)) was significantly higher than other groups (p < 0.01). The grade scores for basal ganglia PVS (BG-PVS) were positively correlated with the degree of DMV (R = 0.67, p < 0.01), rather than centrum semivole PVS (CS-PVS) (R = 0.17, p = 0.1). In multivariate analysis, high CMB burden (adjusted odds ratio [aOR], 25.38; 95% confidence interval [CI], 1.87-345.23) was associated with severe DMV scores. In addition, BG-PVS was related to severe DMV burden in a dose-dependent manner: when BG-PVS score was 3 and 4, the aORs of severe DMV burden were 18.5 and 12.19, respectively.ConclusionThe DMV impairment was associated with the severity of cSVD, which suggests that DMV burden may be used for risk stratification in SVO-AIS patients.Clinical relevance statementThe DMV damage score, based on the association between small vessel disease and the deep medullary veins impairment, is a potential new imaging biomarker for the prognosis of small vessel occlusion acute ischemic stroke, with clinical management implications.Key points• The damage to the deep medullary vein may be one mechanism of cerebral small vessel disease. • Severe burden of the basal ganglia perivascular space and cerebral microbleed is closely associated with significant impairment to the deep medullary vein. • The deep medullary vein damage score may reflect a risk of added vascular damage in small vessel occlusion acute ischemic stroke patients.

Project description: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, 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 23 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.

Dataset Information

APOL1, CDKN2A/CDKN2B, and HDAC9 polymorphisms and small vessel ischemic stroke.

Publications

APOL1, CDKN2A/CDKN2B, and HDAC9 polymorphisms and small vessel ischemic stroke.

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