Epistasis Analysis for Estrogen Metabolic and Signaling Pathway Genes on Young Ischemic Stroke Patients

Yi Chen Hsieh, Jiann Shing Jeng, Huey Juan Lin, Chaur Jong Hu, Chia Chen Yu, Li Ming Lien, Giia Sheun Peng, C. I Chin I Chen, Sung Chun Tang, Nai Fang Chi, Hung Pin Tseng, Chang Ming Chern, F. I Fang I Hsieh, Chyi Huey Bai, Yi Rhu Chen, Hung Yi Chiou, Jiann Shing Jeng, Sung Chun Tang, Shin Joe Yeh, Li Kai TsaiShin Kong, Li Ming Lien, Hou Chang Chiu, Wei Hung Chen, Chyi Huey Bai, Tzu Hsuan Huang, Chi Ieong Lau, Ya Ying Wu, Rey Yue Yuan, Chaur Jong Hu, Jau Jiuan Sheu, Jia Ming Yu, Chun Sum Ho, Chin I. Chen, Jia Ying Sung, Hsing Yu Weng, Yu Hsuan Han, Chun Ping Huang, Wen Ting Chung, Der Shin Ke, Huey Juan Lin, Chia Yu Chang, Poh Shiow Yeh, Kao Chang Lin, Tain Junn Cheng, Chih Ho Chou, Chun Ming Yang, Giia Sheun Peng, Jiann Chyun Lin, Yaw Don Hsu, Jong Chyou Denq, Jiunn Tay Lee, Chang Hung Hsu, Chun Chieh Lin, Che Hung Yen, Chun An Cheng, Yueh Feng Sung, Yuan Liang Chen, Ming Tung Lien, Chung Hsing Chou, Chia Chen Liu, Fu Chi Yang, Yi Chung Wu, An Chen Tso, Yu Hua Lai, Chun I. Chiang, Chia Kuang Tsai, Meng Ta Liu, Ying Che Lin, Yu Chuan Hsu, Chih Hung Chen, Pi Shan Sung, Chang Ming Chern, Han Hwa Hu, Wen Jang Wong, Yun On Luk, Li Chi Hsu, Chih Ping Chung, Hung Pin Tseng, Chin Hsiung Liu, Chun Liang Lin, Hung Chih Lin, Chaur Jong Hu

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


Background: Endogenous estrogens play an important role in the overall cardiocirculatory system. However, there are no studies exploring the hormone metabolism and signaling pathway genes together on ischemic stroke, including sulfotransferase family 1E (SULT1E1), catechol-O-methyl-transferase (COMT), and estrogen receptor α (ESR1). Methods: A case-control study was conducted on 305 young ischemic stroke subjects aged ≦ 50 years and 309 age-matched healthy controls. SULT1E1 -64G/A, COMT Val158Met, ESR1 c.454-397 T/C and c.454-351 A/G genes were genotyped and compared between cases and controls to identify single nucleotide polymorphisms associated with ischemic stroke susceptibility. Gene-gene interaction effects were analyzed using entropy-based multifactor dimensionality reduction (MDR), classification and regression tree (CART), and traditional multiple regression models. Results: COMT Val158Met polymorphism showed a significant association with susceptibility of young ischemic stroke among females. There was a two-way interaction between SULT1E1 -64G/A and COMT Val158Met in both MDR and CART analysis. The logistic regression model also showed there was a significant interaction effect between SULT1E1 -64G/A and COMT Val158Met on ischemic stroke of the young (P for interaction = 0.0171). We further found that lower estradiol level could increase the risk of young ischemic stroke for those who carry either SULT1E1 or COMT risk genotypes, showing a significant interaction effect (P for interaction = 0.0174). Conclusions: Our findings support that a significant epistasis effect exists among estrogen metabolic and signaling pathway genes and gene-environment interactions on young ischemic stroke subjects.

Original languageEnglish
Article numbere47773
JournalPLoS One
Issue number10
Publication statusPublished - Oct 24 2012

ASJC Scopus subject areas

  • General Agricultural and Biological Sciences
  • General Biochemistry,Genetics and Molecular Biology
  • General Medicine


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