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A Case-Control Study and Meta-Analysis of the Association of eNOS rs1799983 SNP with Stroke Risk

Original article

Abstrak

Polimorfisme nitrat sintase endothelial (eNOS) rs1799983 telah dikenalpasti dapat meningkatkan risiko terhadap strok, tetapi tiada data yang dilaporkan dalam negara Malaysia. Oleh itu, kajian ini bertujuan untuk mengkaji perkaitan ini dalam populasi Malaysia dan dalam meta-analisis secara menyeluruh. Pengenotipan eNOS rs1799983 polimorfisme telah dilakukan bagi 241 rakyat Malaysia dengan menggunakan tanda hidrolisis. Nisbah ganjil dengan selang keyakinan 95% telah dikira. Meta-analisis dijalankan dengan perisian Comprehensive Meta-Analysis Ver. 2.2.064. Nilai p kurang daripada 0.05 dianggap signifikan secara statistik. Secara keseluruhannya, kami menunjukkan bahawa alel eNOS rs1799983-T meningkatkan risiko terhadap strok terutamanya dalam kalangan lelaki, mereka yang kerap makan makanan segera dan bangsa Cina Malaysia. Meta-analisis menunjukkan bahawa polimorfisme rs1799983 dikaitkan dengan peningkatan risiko terhadap strok iskemia dalam model resesif dan alelik. Selepas stratifikasi mengikut populasi, perkaitan ini kekal signifikan dalam populasi Asia tetapi tidak signifikan dalam populasi Kaukasia. Kesimpulannya, kajian ini mendapati bahawa terdapat hubungan yang signifikan antara polimorfisme eNOS rs1799983 dengan perbezaan jantina, gaya hidup dan bangsa dalam mempengaruhi risiko terhadap strok di dalam populasi Malaysia. Di samping itu, meta-analisis kami mencadangkan bahawa polimorfisme eNOS rs1799983 dikaitkan dengan peningkatan risiko terhadap strok iskemia.

Abstract

The endothelial nitric oxide synthase (eNOS) rs1799983 polymorphism is known to increase the risk towards stroke, but data is under-reported in Malaysian population. Therefore, this study sought to investigate this association in a Malaysian population and in a comprehensive meta-analysis. Genotyping of the eNOS rs1799983 polymorphism was performed for 241 Malaysians using a hydrolysis probe. Odd ratio with 95% confidence interval was calculated. Meta-analysis was conducted using the Comprehensive Meta-Analysis software ver. 2.2.064. A p-value less than 0.05 was considered statistically significant. Overall, our results showed that the presence of eNOS rs1799983-T allele increases the risk towards stroke, particularly in males, fast-food goers and Malaysian Chinese. The meta-analysis showed that the rs1799983 polymorphism is significantly associated with an increase ischemic stroke risk in the recessive and allelic models. After stratified with population, these associations remain significant in the Asian population but not in the Caucasian population. In summary, this study establishes a significant relationship between the eNOS rs1799983 polymorphism with gender, lifestyle and ethnicity differences towards stroke risk in the Malaysian population. In addition, our meta-analysis suggests that the eNOS rs1799983 polymorphism is associated with an increase risk of ischemic stroke.