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

被引：33

作者：

Akinyemi, Rufus ^{[1
,2
]}

Arnett, Donna K. ^{[3
]}

Tiwari, Hemant K. ^{[4
]}

Ovbiagele, Bruce ^{[5
]}

Sarfo, Fred ^{[6
]}

Srinivasasainagendra, Vinodh ^{[4
]}

Irvin, Marguerite Ryan ^{[4
]}

Adeoye, Abiodun ^{[1
]}

Perry, Rodney T. ^{[4
]}

Akpalu, Albert ^{[7
]}

Jenkins, Carolyn ^{[5
]}

Owolabi, Lukman ^{[8
]}

Obiako, Reginald ^{[9
]}

Wahab, Kolawole ^{[10
]}

Sanya, Emmanuel ^{[10
]}

Komolafe, Morenikeji ^{[11
]}

Fawale, Michael ^{[11
]}

Adebayo, Philip ^{[12
]}

Osaigbovo, Godwin ^{[13
]}

Sunmonu, Taofiki ^{[14
]}

Olowoyo, Paul ^{[15
]}

Chukwuonye, Innocent ^{[16
]}

Obiabo, Yahaya ^{[17
]}

Akpa, Onoja ^{[1
]}

Melikam, Sylvia ^{[1
]}

Saulson, Raelle ^{[5
]}

Kalaria, Raj ^{[18
]}

Ogunniyi, Adesola ^{[1
]}

Owolabi, Mayowa ^{[1
,19
]}

机构：

[1] Univ Ibadan, Ibadan, Nigeria

[2] Fed Med Ctr Abeokuta, Abeokuta, Nigeria

[3] Univ Kentucky, Lexington, KY 40506 USA

[4] Univ Alabama Birmingham, Birmingham, AL USA

[5] Med Univ South Carolina, Charleston, SC 29425 USA

[6] Kwame Nkrumah Univ Sci & Technol, Kumasi, Ghana

[7] Univ Ghana, Med Sch, Accra, Ghana

[8] Aminu Kano Univ, Teaching Hosp, Kano, Nigeria

[9] Ahmadu Bello Univ, Teaching Hosp, Zaria, Nigeria

[10] Univ Ilorin, Teaching Hosp, Ilorin, Nigeria

[11] Obafemi Awolowo Univ, Teaching Hosp, Ife, Nigeria

[12] Ladoke Akintola Univ, Teaching Hosp, Ogbomosho, Nigeria

[13] Jos Univ, Teaching Hosp, Jos, Nigeria

[14] Fed Med Ctr, Owo, Nigeria

[15] Fed Univ, Teaching Hosp Ido Ekiti, Ido Ekiti, Nigeria

[16] Fed Med Ctr, Umuahia, Nigeria

[17] Delta State Univ, Teaching Hosp, Oghara, Nigeria

[18] Newcastle Univ, Newcastle Upon Tyne, Tyne & Wear, England

[19] WFNR Blossom Specialist Med Ctr lbadan, Ibadan, Nigeria

来源：

JOURNAL OF THE NEUROLOGICAL SCIENCES | 2017年 / 379卷

基金：

美国国家卫生研究院;

关键词：

Interleukin-6; Cyclin dependent kinase inhibitor; Candidate gene; lschemic Stroke; West Africa; PROMOTER GENE POLYMORPHISMS; STATISTICS-COMMITTEE; HEART-DISEASE; RISK-FACTORS; INFLAMMATION; POPULATION; PREVALENCE; EXPRESSION; SMOKING; UPDATE;

D O I：

10.1016/j.jns.2017.05.046

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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. (C) 2017 Elsevier B.V. All Tights reserved.

引用

页码：229 / 235

页数：7

共 49 条

[1] Stroke genomics in people of African ancestry: charting new paths [J].

Akinyemi, R. O. ;

Ovbiagele, B. ;

Akpalu, A. ;

Jenkins, C. ;

Sagoe, K. ;

Owolabi, L. ;

Sarfo, F. ;

Obiako, R. ;

Gebreziabher, M. ;

Melikam, E. ;

Warth, S. ;

Arulogun, O. ;

Lackland, D. ;

Ogunniyi, A. ;

Tiwari, H. ;

Kalaria, R. N. ;

Arnett, D. ;

Owolabi, M. O. .

CARDIOVASCULAR JOURNAL OF AFRICA, 2015, 26 (02) :S39-S49

[2] Phenotyping Stroke in Sub-Saharan Africa: Stroke Investigative Research and Education Network (SIREN) Phenomics Protocol [J].

Akpalu, Albert ;

Sarfo, Fred Stephen ;

Ovbiagele, Bruce ;

Akinyemi, Rufus ;

Gebregziabher, Mulugeta ;

Obiako, Reginald ;

Owolabi, Lukman ;

Sagoe, Kwamena ;

Jenkins, Carolyn ;

Arulogun, Oyedunni ;

Adamu, Sheila ;

Appiah, Lambert T. ;

Adadey, Martin A. ;

Agyekum, Francis ;

Quansah, Joseph A. ;

Mensah, Yaw B. ;

Adeoye, Abiodun M. ;

Singh, Arti ;

Tosin, Aridegbe O. ;

Ohifemen, Osimhiarherhuo ;

Sani, Abubabkar A. ;

Tabi-Ajayi, Eric ;

Phillip, Ibinaiye O. ;

Isah, Suleiman Y. ;

Tabari, Nasir A. ;

Mande, Aliyu ;

Agunloye, Atinuke M. ;

Ogbole, Godwin I. ;

Akinyemi, Joshua O. ;

Akpa, Onoja M. ;

Laryea, Ruth ;

Melikam, Sylvia Ezinne ;

Adinku, Dorcas ;

Uvere, Ezinne ;

Burkett, Nina-Serena ;

Adekunle, Gregory F. ;

Kehinde, Salaam I. ;

Azuh, Paschal C. ;

Dambatta, Abdul H. ;

Ishaq, Naser A. ;

Arnett, Donna ;

Tiwari, Hemant K. ;

Lackland, Dan ;

Owolabi, Mayowa .

NEUROEPIDEMIOLOGY, 2015, 45 (02) :73-82

[3] Neurogenomics in Africa: Perspectives, progress, possibilities and priorities [J].

Aldnyemi, Rufus O. ;

Owolabi, Mayowa O. ;

Oyeniyi, Tolulope ;

Ovbiagele, Bruce ;

Arnett, Donna K. ;

Tiwari, Hemant K. ;

Walker, Richard ;

Ogunniyi, Adesola ;

Kalaria, Raj N. .

JOURNAL OF THE NEUROLOGICAL SCIENCES, 2016, 366 :213-223

[4] THE PROBABILITY FUNCTION OF THE PRODUCT OF 2 NORMALLY DISTRIBUTED VARIABLES [J].

AROIAN, LA .

ANNALS OF MATHEMATICAL STATISTICS, 1947, 18 (02) :265-271

[5] Association of the APOE, MTHFR and ACE genes polymorphisms and stroke in Zambian patients [J].

Atadzhanov, Masharip ;

Mwaba, Mwila H. ;

Mukomena, Patrice N. ;

Lakhi, Shabir ;

Rayaprolu, Sruti ;

Ross, Owen A. ;

Meschia, James F. .

NEUROLOGY INTERNATIONAL, 2013, 5 (04) :69-72

[6] Sex Differences in Stroke Incidence, Prevalence, Mortality and Disability-Adjusted Life Years: Results from the Global Burden of Disease Study 2013 [J].

Barker-Collo, Suzanne ;

Bennett, Derrick A. ;

Krishnamurthi, Rita V. ;

Parmar, Priya ;

Feigin, Valery L. ;

Naghavi, Mohsen ;

Forouzanfar, Mohammed H. ;

Johnson, Catherine O. ;

Nguyen, Grant ;

Mensah, George A. ;

Vos, Theo ;

Murray, Christopher J. L. ;

Roth, Gregory A. .

NEUROEPIDEMIOLOGY, 2015, 45 (03) :203-214

[7]

Biffi A, LANCET NEUROL, P702, DOI [10.1016/S474-4422(11)70148-X, DOI 10.1016/S474-4422(11)70148-X]

[8] Meta-Analysis of Genome-Wide Association Studies Identifies Genetic Risk Factors for Stroke in African Americans [J].

Carty, Cara L. ;

Keene, Keith L. ;

Cheng, Yu-Ching ;

Meschia, James F. ;

Chen, Wei-Min ;

Nalls, Mike ;

Bis, Joshua C. ;

Kittner, Steven J. ;

Rich, Stephen S. ;

Tajuddin, Salman ;

Zonderman, Alan B. ;

Evans, Michele K. ;

Langefeld, Carl D. ;

Gottesman, Rebecca ;

Mosley, Thomas H. ;

Shahar, Eyal ;

Woo, Daniel ;

Yaffe, Kristine ;

Liu, Yongmei ;

Sale, Michele M. ;

Dichgans, Martin ;

Malik, Rainer ;

Longstreth, W. T., Jr. ;

Mitchell, Braxton D. ;

Psaty, Bruce M. ;

Kooperberg, Charles ;

Reiner, Alexander ;

Worrall, Bradford B. ;

Fornage, Myriam .

STROKE, 2015, 46 (08) :2063-2068

[9] Inflammation-mediated damage in progressing lacunar infarctions -: A potential therapeutic target [J].

Castellanos, M ;

Castillo, J ;

García, MM ;

Leira, R ;

Serena, J ;

Chamorro, A ;

Dávalos, A .

STROKE, 2002, 33 (04) :982-987

[10] Sickle Cell Trait and Incident Ischemic Stroke in the Atherosclerosis Risk in Communities Study [J].

Caughey, Melissa C. ;

Loehr, Laura R. ;

Key, Nigel S. ;

Derebail, Vimal K. ;

Gottesman, Rebecca F. ;

Kshirsagar, Abhijit V. ;

Grove, Megan L. ;

Heiss, Gerardo .

STROKE, 2014, 45 (10) :2863-2867

← 1 2 3 4 5 →