Interleukin-6 (IL-6) rs1800796 and cyclin dependent kinase inhibitor (CDKN2A/CDKN2B) rs2383207 are associated with ischemic stroke in indigenous West African Men.

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.

• Authors: Rufus Akinyemi, Donna K Arnett, Hemant K Tiwari, Bruce Ovbiagele, Fred Sarfo, Vinodh Srinivasasainagendra, Marguerite Ryan Irvin, Abiodun Adeoye, Rodney T Perry, Albert Akpalu, Carolyn Jenkins, Lukman Owolabi, Reginald Obiako, Kolawole Wahab, Emmanuel Sanya, Morenikeji Komolafe, Michael Fawale, Philip Adebayo, Godwin Osaigbovo, Taofiki Sunmonu, Paul Olowoyo, Innocent Chukwuonye, Yahaya Obiabo, Onoja Akpa, Sylvia Melikam, Raelle Saulson, Raj Kalaria, Adesola Ogunniyi, Mayowa Owolabi, SIREN Investigators
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 379 Pg. 229-235 (Aug 15 2017) ISSN: 1878-5883 [Electronic] Netherlands
• PMID: 28716248 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• CDKN2A protein, human
• CDKN2B protein, human
• Cyclin-Dependent Kinase Inhibitor p15
• Cyclin-Dependent Kinase Inhibitor p16
• Cyclin-Dependent Kinase Inhibitor p18
• IL6 protein, human
• Interleukin-6

Topics

• Black People (genetics)
• Brain Ischemia (complications, genetics)
• Case-Control Studies
• Cyclin-Dependent Kinase Inhibitor p15 (genetics)
• Cyclin-Dependent Kinase Inhibitor p16
• Cyclin-Dependent Kinase Inhibitor p18 (genetics)
• Female
• Genetic Predisposition to Disease (genetics)
• Humans
• Interleukin-6 (genetics)
• Male
• Middle Aged
• Polymorphism, Single Nucleotide (genetics)
• Sex Factors
• Stroke (complications, genetics)