Rufus Akinyemi1, Donna K Arnett2, Hemant K Tiwari3, Bruce Ovbiagele4, Fred Sarfo5, Vinodh Srinivasasainagendra3, Marguerite Ryan Irvin3, Abiodun Adeoye6, Rodney T Perry3, Albert Akpalu7, Carolyn Jenkins8, Lukman Owolabi9, Reginald Obiako10, Kolawole Wahab11, Emmanuel Sanya11, Morenikeji Komolafe12, Michael Fawale12, Philip Adebayo13, Godwin Osaigbovo14, Taofiki Sunmonu15, Paul Olowoyo16, Innocent Chukwuonye17, Yahaya Obiabo18, Onoja Akpa6, Sylvia Melikam6, Raelle Saulson8, Raj Kalaria19, Adesola Ogunniyi6, Mayowa Owolabi20. 1. University of Ibadan, Ibadan, Nigeria; Federal Medical Centre Abeokuta, Nigeria. 2. University of Kentucky, KY, USA. 3. University of Alabama at Birmingham, Birmingham, USA. 4. Medical University of South Carolina, SC, USA.. Electronic address: ovibes@musc.edu. 5. Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. 6. University of Ibadan, Ibadan, Nigeria. 7. University of Ghana Medical School, Accra, Ghana. 8. Medical University of South Carolina, SC, USA. 9. Aminu Kano University Teaching Hospital, Kano, Nigeria. 10. Ahmadu Bello University Teaching Hospital, Zaria, Nigeria. 11. University of Ilorin Teaching Hospital, Ilorin, Nigeria. 12. Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria. 13. Ladoke Akintola University Teaching Hospital, Ogbomosho, Nigeria. 14. Jos University Teaching Hospital, Jos, Nigeria. 15. Federal Medical Centre, Owo, Nigeria. 16. Federal University Teaching Hospital Ido-Ekiti, Nigeria. 17. Federal Medical Centre, Umuahia, Nigeria. 18. Delta State University Teaching Hospital, Oghara, Nigeria. 19. Newcastle University, Newcastle upon Tyne, UK. 20. University of Ibadan, Ibadan, Nigeria; WFNR-Blossom Specialist Medical Center Ibadan, Nigeria.
Abstract
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.
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.
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