白细胞介素-6（IL-6）基因rs1800796和细胞周期蛋白依赖性激酶抑制剂（CDKN2A/CDKN2B）基因rs2383207与西非本土男性的缺血性中风有关。
Interleukin-6 (IL-6) rs1800796 and cyclin dependent kinase inhibitor (CDKN2A/CDKN2B) rs2383207 are associated with ischemic stroke in indigenous West African Men.
作者信息
Akinyemi Rufus, Arnett Donna K, Tiwari Hemant K, Ovbiagele Bruce, Sarfo Fred, Srinivasasainagendra Vinodh, Irvin Marguerite Ryan, Adeoye Abiodun, Perry Rodney T, Akpalu Albert, Jenkins Carolyn, Owolabi Lukman, Obiako Reginald, Wahab Kolawole, Sanya Emmanuel, Komolafe Morenikeji, Fawale Michael, Adebayo Philip, Osaigbovo Godwin, Sunmonu Taofiki, Olowoyo Paul, Chukwuonye Innocent, Obiabo Yahaya, Akpa Onoja, Melikam Sylvia, Saulson Raelle, Kalaria Raj, Ogunniyi Adesola, Owolabi Mayowa
机构信息
University of Ibadan, Ibadan, Nigeria; Federal Medical Centre Abeokuta, Nigeria.
University of Kentucky, KY, USA.
出版信息
J Neurol Sci. 2017 Aug 15;379:229-235. doi: 10.1016/j.jns.2017.05.046. Epub 2017 May 23.
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.
背景
遗传变异为撒哈拉以南非洲人群中观察到的中风特殊性提供了一种可能的解释。白细胞介素 - 6多态性先前已在一些非非洲人群中与缺血性中风相关联。
目的
在此，我们首次在中风调查研究与教育网络（SIREN）研究的西非本土参与者中，调查白细胞介素 - 6、CDKN2A - CDKN2B及其他基因的遗传多态性与缺血性中风之间的关联。
方法
对14个与缺血性中风神经生物学相关基因中先前确定的23个单核苷酸多态性（SNP）进行了研究。构建了针对已知心血管疾病风险因素进行调整的逻辑回归模型，以评估这23个SNP在经过严格表型分型的缺血性中风病例（N = 429）（男性 = 198；女性 = 231）和无中风（N = 483）对照（男性 = 236；女性 = 247）中的关联。
结果
白细胞介素 - 6（IL6）rs1800796（C为次要等位基因；频率：西非人为8.6%）在模型中与患有高血压的男性缺血性中风显著相关（比值比 = 2.006，95%置信区间 = [1.065, 3.777]，p = 0.031），但在女性中不相关。此外，CDKN2A/CDKN2B中的rs2383207（次要等位基因A，频率：西非人为1.7%）在模型中有主要协变量的情况下也与男性缺血性中风相关（比值比 = 2.550，95%置信区间 = [1.027, 6.331]，p = 0.044），但在女性中不相关。其他基因的多态性与缺血性中风未显示出显著关联。
结论
IL6基因中的rs1800796多态性和CDKN2A/CDKN2B基因中的rs2383207多态性与西非本土男性缺血性中风显著相关。CDKN2A/CDKN2B SNP rs2383207与西非本土男性缺血性中风独立相关。进一步的研究应关注炎症基因和其他遗传多态性的作用，以及性别对非洲裔人群中风神经生物学的影响。
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