Center for Genomic and Precision Medicine, University of Ibadan, Ibadan, Nigeria.
Federal Medical Centre Abeokuta, Ibadan, Nigeria.
Acta Neurol Scand. 2018 Jan;137(1):133-141. doi: 10.1111/ane.12847. Epub 2017 Oct 3.
Worldwide, the highest frequencies of APOL1-associated kidney variants are found in indigenous West Africans among whom small vessel disease (SVD) ischemic stroke is the most common stroke phenotype. The objective of this study was to investigate the association and effect sizes of 23 selected SNPs in 14 genes of relevance, including the APOL1 G1 variants, with the occurrence of SVD ischemic stroke among indigenous West African participants in the Stroke Investigative Research and Education Network (SIREN) Study.
Cases were consecutively recruited consenting adults (aged 18 years or older) with neuroimaging-confirmed first clinical stroke. Stroke-free controls were ascertained using a locally validated version of the Questionnaire for Verifying Stroke-Free Status (QVSFS). Logistic regression models adjusting for known vascular risk factors were fitted to assess the associations of the 23 SNPs in rigorously phenotyped cases (N = 154) of SVD ischemic stroke and stroke-free (N = 483) controls.
Apolipoprotein L1 (APOL1) rs73885319 (OR = 1.52; CI: 1.09-2.13, P-value = .013), rs2383207 in CDKN2A/CDKN2B (OR = 3.08; CI: 1.15-8.26, P -value = .026) and rs2107595 (OR = 1.70; CI: 1.12-2.60, P-value = .014) and rs28688791 (OR = 1.52; CI: 1.03-2.26, P-value = .036) in HDAC9 gene were associated with SVD stroke at 0.05 significance level. Polymorphisms in other genes did not show significant associations.
This is the first report of a specific association of APOL1 with a stroke subtype. Further research is needed to confirm these initial findings and deepen understanding of the genetics of stroke in people of African ancestry with possible implications for other ancestries as all humans originated from Africa.
在全球范围内，APOL1 相关肾脏变异体的最高频率出现在非洲裔土著人中，其中小血管疾病 (SVD) 缺血性卒中是最常见的卒中表型。本研究的目的是调查与非洲裔土著人西非人中风血管性危险因素相关的 14 个基因中的 23 个选定单核苷酸多态性 (SNP) 的相关性和效应大小，包括 APOL1 G1 变体，这些变体与中风血管性危险因素相关在中风调查研究与教育网络 (SIREN) 研究中的 SVD 缺血性卒中的发生。
连续招募同意的成年病例（年龄在 18 岁或以上），并进行神经影像学证实的首次临床卒中。使用经过本地验证的中风状态验证问卷 (QVSFS) 确定无卒中对照。对严格表型化的 SVD 缺血性卒中病例 (n = 154) 和无卒中对照 (n = 483) 进行 logistic 回归模型调整以评估 23 个 SNP 的相关性。
载脂蛋白 L1 (APOL1) rs73885319(OR = 1.52；CI: 1.09-2.13，P 值 = 0.013)、CDKN2A/CDKN2B 中的 rs2383207(OR = 3.08；CI: 1.15-8.26，P 值 = 0.026)和 rs2107595(OR = 1.70；CI: 1.12-2.60，P 值 = 0.014)以及 HDAC9 基因中的 rs28688791(OR = 1.52；CI: 1.03-2.26，P 值 = 0.036)与 SVD 卒中在 0.05 显著水平相关。其他基因中的多态性没有显示出显著相关性。
这是首次报道 APOL1 与卒中亚型的特定关联。需要进一步研究来证实这些初步发现，并加深对非洲裔人群中卒中遗传学的理解，这可能对其他血统的人具有影响，因为所有人类都起源于非洲。
