Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Jan;137(1):133-141.
doi: 10.1111/ane.12847. Epub 2017 Oct 3.

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

R Akinyemi  1   2 , H K Tiwari  3 , D K Arnett  4 , B Ovbiagele  5 , M R Irvin  3 , K Wahab  6 , F Sarfo  7 , V Srinivasasainagendra  3 , A Adeoye  1 , R T Perry  3 , A Akpalu  8 , C Jenkins  5 , O Arulogun  1 , M Gebregziabher  5 , L Owolabi  9 , R Obiako  10 , E Sanya  6 , M Komolafe  11 , M Fawale  11 , P Adebayo  12 , G Osaigbovo  13 , T Sunmonu  14 , P Olowoyo  15 , I Chukwuonye  16 , Y Obiabo  17 , A Onoja  18 , J Akinyemi  18 , G Ogbole  19 , S Melikam  1 , R Saulson  5 , M Owolabi  1   20 ; SIREN Investigators
Affiliations

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

R Akinyemi et al. Acta Neurol Scand. 2018 Jan.

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.

Keywords: APOL1; African Ancestry; CDKN2A/CDKN2B; HDAC9; West Africa; candidate genes; small vessel disease; stroke.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest: The authors report no conflicts of interest

References

    1. Feigin VL, Roth GA, Naghavi M, et al. Global burden of stroke and risk factors in 188 countries, during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. The Lancet Neurology. 2016;15:913–24. - PubMed
    1. Lanktree MB, Dichgans M, Hegele RA. Advances in genomic analysis of stroke: what have we learned and where are we headed? Stroke; a journal of cerebral circulation. 2010;41:825–32. - PubMed
    1. Howard VJ, Kleindorfer DO, Judd SE, et al. Disparities in stroke incidence contributing to disparities in stroke mortality. Annals of neurology. 2011;69:619–27. - PMC - PubMed
    1. Collins FS. What we do and don’t know about ‘race’, ‘ethnicity’, genetics and health at the dawn of the genome era. Nature genetics. 2004;36:S13–5. - PubMed
    1. Douiri A, Rudd AG, Wolfe CD. Prevalence of poststroke cognitive impairment: South London Stroke Register 1995–2010. Stroke; a journal of cerebral circulation. 2013;44:138–45. - PubMed