Objectives

The relationships of Paired Like Homeodomain 2 (PITX2), Ninjurin 2 (NINJ2), TWIST-Related Protein 1 (TWIST1), Ras Interacting Protein 1 (Rasip1), Solute Carrier Family 17 Member 3 (SLC17A3), Methylmalonyl Co-A Mutase (MUT) and Fer3 Like BHLH Transcription Factor (FERD3L) polymorphisms and gene expression with ischemic stroke have yet to be determined in Malaysia. Hence, this study aimed to explore the associations of single nucleotide polymorphisms (SNPs) and gene expression with ischemic stroke risk among population who resided at the Northern region of Malaysia.

Materials and methods

Study subjects including 216 ischemic stroke patients and 203 healthy controls were recruited upon obtaining ethical clearance. SNP genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism assays. Gene expression levels were quantified by real-time polymerase chain reaction assays. Statistical and genetic analyses were conducted with SPSS version 22.2, PLINK version 1.07 and multifactor dimensionality reduction software.

Results

Study subjects with G allele, CG or GG genotypes of SLC17A3 rs9379800 demonstrated increased risk of ischemic stroke with the odds ratios ranging from 1.76-fold to 3.14-fold (p<0.05). When stratified study subjects according to the ethnicity, SLC17A3 rs9379800 G allele and CG genotype contributed to 2.14- and 2.96-fold of ischemic stroke risk among Malay population significantly, in the multivariate analysis (p<0.05). However, no significant associations were observed for PITX2, NINJ2, TWIST1, Rasip1, and MUT polymorphisms with ischemic stroke risk in the multivariate analysis for the pooled cases and controls as well as when stratified them according to the ethnicity. Lower mRNA expression levels of Rasip1, SLC17A3, MUT and FERD3L were observed among cases (p<0.05). After FDR adjustment, the mRNA level of SLC17A3 remained significantly associated with ischemic stroke among Malay population (q=0.034).

Conclusion

In conclusion, this study suggests that SLC17A3 rs9379800 polymorphism and its gene expression contribute to significant ischemic stroke risk among Malaysian population, particularly the Malay who resided at the Northern Region of the country. Our findings can provide useful information for the future diagnosis, management and treatment of ischemic stroke patients.

中文翻译：

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SLC17A3 rs9379800 和马来西亚北部地区的缺血性中风易感性

目标

的关系配对就像同源域2（PITX2），Ninjurin 2（NINJ2），TWIST相关蛋白1（TWIST1），拉斯相互作用蛋白1（Rasip1），溶质载体家族17成员3（SLC17A3），甲基丙辅酶A变位酶（MUT ) 和Fer3 Like BHLH 转录因子( FERD3L) 缺血性中风的多态性和基因表达尚未在马来西亚确定。因此，本研究旨在探讨居住在马来西亚北部地区的人群中单核苷酸多态性 (SNP) 和基因表达与缺血性中风风险之间的关联。

材料和方法

在获得伦理许可后招募了包括 216 名缺血性中风患者和 203 名健康对照在内的研究对象。SNP 基因分型是使用聚合酶链反应限制性片段长度多态性分析进行的。基因表达水平通过实时聚合酶链反应测定进行量化。使用SPSS 22.2版、PLINK 1.07版和多因素降维软件进行统计和遗传分析。

结果

具有SLC17A3 rs9379800 的G 等位基因、CG 或 GG 基因型的研究对象表现出缺血性中风的风险增加，优势比范围为 1.76 倍至 3.14 倍（p<0.05）。当根据种族对研究对象进行分层时，在多变量分析中，SLC17A3 rs9379800 G 等位基因和 CG 基因型显着增加了马来人人群缺血性卒中风险的 2.14 倍和 2.96 倍（p<0.05）。然而，在合并病例和对照的多变量分析以及根据种族对它们进行分层时，未观察到PITX2、NINJ2、TWIST1、Rasip1和MUT多态性与缺血性卒中风险的显着关联。降低Rasip1、SLC17A3、MUT 的mRNA 表达水平在病例中观察到FERD3L和FERD3L（p<0.05）。FDR 调整后，SLC17A3的 mRNA 水平仍然与马来人群的缺血性中风显着相关（q=0.034）。

结论

总之，这项研究表明，SLC17A3 rs9379800 多态性及其基因表达导致马来西亚人群，尤其是居住在该国北部地区的马来人发生显着的缺血性中风风险。我们的研究结果可为缺血性卒中患者未来的诊断、管理和治疗提供有用的信息。