TY - JOUR
T1 - Interleukin–6 (IL-6) rs1800796 and cyclin dependent kinase inhibitor (CDKN2A/CDKN2B) rs2383207 are associated with ischemic stroke in indigenous West African Men
AU - for the SIREN Investigators
AU - Akinyemi, Rufus
AU - Arnett, Donna K.
AU - Tiwari, Hemant K.
AU - Ovbiagele, Bruce
AU - Sarfo, Fred
AU - Srinivasasainagendra, Vinodh
AU - Irvin, Marguerite Ryan
AU - Adeoye, Abiodun
AU - Perry, Rodney T.
AU - Akpalu, Albert
AU - Jenkins, Carolyn
AU - Owolabi, Lukman
AU - Obiako, Reginald
AU - Wahab, Kolawole
AU - Sanya, Emmanuel
AU - Komolafe, Morenikeji
AU - Fawale, Michael
AU - Adebayo, Philip
AU - Osaigbovo, Godwin
AU - Sunmonu, Taofiki
AU - Olowoyo, Paul
AU - Chukwuonye, Innocent
AU - Obiabo, Yahaya
AU - Akpa, Onoja
AU - Melikam, Sylvia
AU - Saulson, Raelle
AU - Kalaria, Raj
AU - Ogunniyi, Adesola
AU - Owolabi, Mayowa
N1 - Funding Information:
The SIREN project is supported by U54HG007479 from the National Institutes of Health (NIH) as part of the H3Africa Consortium.
Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017/8/15
Y1 - 2017/8/15
N2 - 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.
AB - 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.
KW - Candidate gene
KW - Cyclin dependent kinase inhibitor
KW - Interleukin-6
KW - Ischemic Stroke
KW - West Africa
UR - http://www.scopus.com/inward/record.url?scp=85021064223&partnerID=8YFLogxK
U2 - 10.1016/j.jns.2017.05.046
DO - 10.1016/j.jns.2017.05.046
M3 - Article
C2 - 28716248
AN - SCOPUS:85021064223
SN - 0022-510X
VL - 379
SP - 229
EP - 235
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
ER -