Association study of polymorphisms in the ABO gene with ischemic stroke in the Chinese population

Ling et al. BMC Neurology (2016) 16:146 DOI 10.1186/s12883-016-0671-7 RESEARCH ARTICLE Open Access Association study of polymorphisms in the ABO gene with ischemic stroke in the Chinese population Xiaoming Ling1†, Yansong Zheng2†, Jing Tao3,4, Zhezhou Zheng5 and Lidian Chen6* Abstract Background: Ischemic stroke is the main cause of mortality and disability in older people worldwide. Recently epidemiological studies indicate that ischemic stroke is a complex disorder with a strong genetic component. Genome-wide association studies (GWAS) identified several single nucleotide polymorphisms (SNPs) associated with coronary artery disease (CAD) and myocardial infarction (MI) locus in ABO gene. Our study examined the association between four variants in the ABO gene and the risk of ischemic stroke and its subtypes, large-artery atherosclerosis (LAA) and small-vessel diseases (SVD) in the Chinese population. Methods: In this case–control study, we recruited 1897 subjects, including 979 healthy controls and 918 ischemic stroke patients (465 with LAA and 453 with SVD). We selected four single nucleotide polymorphisms (rs579459, rs651007, rs514659 and rs529565) of the ABO gene and performed genotyping assays to assess the association with ischemic stroke and its subtypes. Results: We found three polymorphisms, rs579459 and rs651007 were significantly associated with LAA using additive model and rs529565 was significantly associated with LAA using additive and dominant models. And we failed to find any significant association between these SNPs and ischemic stroke and SVD in the Chinese population. However, after the Bonferroni correction for multiple comparisons, the P-values of these SNPs failed to exceed significant threshold under any models. Conclusion: Our findings indicated that genetic variations of ABO gene may contribute to susceptibility of LAA but not ischemic stroke and SVD in the Chinese population. Our preliminary results should be further validated in prospective independent studies with expanded sample size. Keywords: Ischemic stroke, ABO, Single nucleotide polymorphism, Association study Abbreviations: SNP, Single nucleotide polymorphism; GWAS, Genome-wide association studies; CAD, Coronary artery disease; MI, Myocardial infarction; LAA, Large-artery atherosclerosis; SVD, Small-vessel diseases; VTE, Venous thromboembolism; CT, Computed tomography; MRI, Magnetic resonance imaging; LD, Linkage disequilibrium; HWE, Hardy-Weinberg equilibrium tests; OR, Odds ratio; CI, Confidence interval Background Stroke is one of the main causes of death and adult disability around the world [1, 2]. There are two major categories of stroke: ischemic stroke and hemorrhagic stroke, and ischemic stroke constitutes over 80 % of total stroke in origin [3]. Increasing evidence indicated that * Correspondence: † Equal contributors 6 Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China Full list of author information is available at the end of the article ischemic stroke is a complex clinical syndrome resulting from environmental and genetic factors [4, 5]. According to the modified Trial of Org10172 in Acute Stroke Treatment (TOAST) classification,ischemic stroke itself can be divided into five subtypes, LAA and SVD are two common etiologic subtypes of ischemic stroke [6, 7]. Conventional risk factors such as hypertension, diabetes mellitus, dyslipidemia and smoking could not completely explain all ischemic stroke risk, family and twin-based © 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Ling et al. BMC Neurology (2016) 16:146 studies demonstrated that genetic factors also play a key role in the development of ischemic stroke [8, 9]. The ABO gene, located around 9q34.2, encodes glycosyltransferases, which catalyze the transfer to different carbohydrate groups onto the H antigen, thus forming A and B antigens of the ABO system [10, 11]. In recent years, several studies have found that genetic variants of ABO gene were associated with several diseases. Previous studies have identified rs579459 in ABO as genetic variants associated with the risk of CAD in European descent [12]. Recent study also identified the ABO rs579459 polymorphism as genetic variants significantly associated with venous thromboembolism (VTE) [13]. However, fewer studies focus on the association between ABO gene and ischemic stroke [14–16]. Ischemic stroke and CAD have several common risk factors and genetic susceptibility, especially for LAA and CAD. Taking all these considerations together, the ABO gene may be a promising candidate gene of ischemic stroke. Recent GWAS showed that three SNPs (rs505922, rs643434, and rs651007) of ABO gene were associated with ischemic stroke and its subtypes in the European population [15]. However, there were no independent replication studies regarding the association between ABO gene and ischemic stroke in Chinese population. Against this background, in the present study we aimed to investigate the association between four SNPs (rs579459, rs651007, rs514659 and rs529565) of ABO gene and ischemic stroke susceptibility in the Chinese population. Methods Subjects Our study sample recruited 979 healthy controls and 918 ischemic stroke patients, including 465 with LAA and 453 with SVD who presented consecutively to the Second People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fujian Provincial Hospital, Fuzhou General Hospital of Nanjing Military Command and Fujian University of Traditional Chinese Medicine Subsidiary Rehabilitation Hospital during August 2013 to December 2014. The Second People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine as a leader of the organization jointed three other hospitals to collect the object of study. All case and control subjects were unrelated to one another and were recruited from the Chinese population. Clinical diagnoses of ischemic stroke were confirmed through computed tomography (CT) and/or magnetic resonance imaging (MRI) scans of the brain. The brain images were independently assessed by two welltrained technologist and physician. The common subtypes (LAA and SVD) of ischemic stroke were Page 2 of 6 determined by the modified TOAST classification system [6]. Control subjects were recruited from the health management of the Second People’s Hospital Affiliated to Fujian University of Traditional Chinese (...truncated)