Li Hao, Cai Yong, Xu An-Ding
Department of Neurology, the First Affiliated Hospital, Jinan University, Guangzhou, China.
Department of Neurology, The People's Hospital of Maoming, Maoming, China.
J Clin Lab Anal. 2018 May;32(4):e22329. doi: 10.1002/jcla.22329. Epub 2017 Oct 6.
To investigate the impact of 4 single nucleotide polymorphisms (SNPs) within ABO gene and their gene-gene interactions on ischemic stroke (IS) susceptibility in Chinese Han population.
A total of 1993 participants (1375 males, 618 females) were selected, including 991 IS patients and 1002 normal controls. The SNPstats (http://bioinfo.iconcologia.net/SNPstats) was used for Hardy-Weinberg equilibrium (HWE) test. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among 4 SNPs within ABO gene. Logistic regression was performed to calculate the ORs (95%CI) for interaction between SNPs.
Both rs579459 and rs505922 within ABO gene were associated with IS risk in additive and dominant models. IS risks were higher in those with minor alleles of rs579459 and rs505922 than those with wild-type homozygotes, OR (95%CI) were 1.62 (1.19-2.10) and 1.69 (1.23-2.18), respectively. We did not find any relation of rs651007 and rs529565 with IS risk in both additive and dominant models. GMDR model indicated a significant two-locus model (P = .0010) involving rs505922 and rs579459, indicating a potential interaction between rs505922 and rs579459, the cross-validation consistency of the two-locus models was 9/10, and the testing accuracy was 60.72%. We also found that participants with rs505922- TC/CC and rs579459- TC/CC genotype have the highest IS risk, compared to participants with rs505922- TT and rs579459- TT genotype, OR (95%CI) was 2.94 (1.28-4.66).
We found that rs579459 and rs505922 within ABO gene and their interaction were both associated with increased IS risk in Chinese population.
研究ABO基因内4个单核苷酸多态性（SNP）及其基因-基因相互作用对中国汉族人群缺血性卒中（IS）易感性的影响。
共选取1993名参与者（男性1375名，女性618名），包括991例IS患者和1002名正常对照。使用SNPstats（http://bioinfo.iconcologia.net/SNPstats）进行哈迪-温伯格平衡（HWE）检验。采用广义多因素降维法（GMDR）筛选ABO基因内4个SNP之间的最佳相互作用组合。进行逻辑回归计算SNP之间相互作用的比值比（OR）及其95%置信区间（95%CI）。
ABO基因内的rs579459和rs505922在相加模型和显性模型中均与IS风险相关。携带rs579459和rs505922次要等位基因者的IS风险高于野生型纯合子，OR（95%CI）分别为1.62（1.19 - 2.10）和1.69（1.23 - 2.18）。在相加模型和显性模型中，未发现rs651007和rs529565与IS风险存在任何关联。GMDR模型显示涉及rs505922和rs579459的两位点模型具有显著性（P = 0.0010），表明rs505922和rs579459之间存在潜在相互作用，两位点模型的交叉验证一致性为9/10，检验准确性为60.72%。我们还发现，与携带rs505922 - TT和rs579459 - TT基因型的参与者相比，携带rs505922 - TC/CC和rs579459 - TC/CC基因型的参与者IS风险最高，OR（95%CI）为2.94（1.28 - 4.66）。
我们发现ABO基因内的rs579459和rs505922及其相互作用均与中国人群IS风险增加相关。
