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 Tsai; Shin 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

doi:10.1371/journal.pone.0047773

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 journal › Article › peer-review

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Abstract

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 language	English
Article number	e47773
Journal	PLoS One
Volume	7
Issue number	10
DOIs	https://doi.org/10.1371/journal.pone.0047773
Publication status	Published - Oct 24 2012

ASJC Scopus subject areas

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

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Hsieh, Y. C., Jeng, J. S., Lin, H. J., Hu, C. J., Yu, C. C., Lien, L. M., Peng, G. S., Chen, C. I. C. I., Tang, S. C., Chi, N. F., Tseng, H. P., Chern, C. M., Hsieh, F. I. F. I., Bai, C. H., Chen, Y. R., Chiou, H. Y., Jeng, J. S., Tang, S. C., Yeh, S. J., ... Hu, C. J. (2012). Epistasis Analysis for Estrogen Metabolic and Signaling Pathway Genes on Young Ischemic Stroke Patients. PLoS One, 7(10), Article e47773. https://doi.org/10.1371/journal.pone.0047773

Hsieh, YC, Jeng, JS, Lin, HJ, Hu, CJ, Yu, CC, Lien, LM, Peng, GS, Chen, CICI, Tang, SC, Chi, NF, Tseng, HP, Chern, CM, Hsieh, FIFI , Bai, CH, Chen, YR, Chiou, HY, Jeng, JS, Tang, SC, Yeh, SJ, Tsai, LK, Kong, S, Lien, LM, Chiu, HC, Chen, WH, Bai, CH, Huang, TH, Lau, CI, Wu, YY, Yuan, RY, Hu, CJ, Sheu, JJ, Yu, JM, Ho, CS, Chen, CI, Sung, JY , Weng, HY, Han, YH, Huang, CP, Chung, WT, Ke, DS, Lin, HJ, Chang, CY, Yeh, PS, Lin, KC, Cheng, TJ, Chou, CH, Yang, CM, Peng, GS, Lin, JC, Hsu, YD, Denq, JC, Lee, JT, Hsu, CH, Lin, CC, Yen, CH, Cheng, CA, Sung, YF, Chen, YL, Lien, MT, Chou, CH, Liu, CC, Yang, FC, Wu, YC, Tso, AC, Lai, YH, Chiang, CI, Tsai, CK, Liu, MT, Lin, YC, Hsu, YC, Chen, CH, Sung, PS, Chern, CM, Hu, HH, Wong, WJ, Luk, YO, Hsu, LC, Chung, CP, Tseng, HP, Liu, CH, Lin, CL, Lin, HC & Hu, CJ 2012, 'Epistasis Analysis for Estrogen Metabolic and Signaling Pathway Genes on Young Ischemic Stroke Patients', PLoS One, vol. 7, no. 10, e47773. https://doi.org/10.1371/journal.pone.0047773

@article{193d41b479f64ac5b548c8d0553ee631,

title = "Epistasis Analysis for Estrogen Metabolic and Signaling Pathway Genes on Young Ischemic Stroke Patients",

abstract = "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.",

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

year = "2012",

month = oct,

day = "24",

doi = "10.1371/journal.pone.0047773",

language = "English",

volume = "7",

journal = "PLoS One",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "10",

}

TY - JOUR

T1 - Epistasis Analysis for Estrogen Metabolic and Signaling Pathway Genes on Young Ischemic Stroke Patients

AU - Hsieh, Yi Chen

AU - Jeng, Jiann Shing

AU - Lin, Huey Juan

AU - Hu, Chaur Jong

AU - Yu, Chia Chen

AU - Lien, Li Ming

AU - Peng, Giia Sheun

AU - Chen, C. I Chin I

AU - Tang, Sung Chun

AU - Chi, Nai Fang

AU - Tseng, Hung Pin

AU - Chern, Chang Ming

AU - Hsieh, F. I Fang I

AU - Bai, Chyi Huey

AU - Chen, Yi Rhu

AU - Chiou, Hung Yi

AU - Jeng, Jiann Shing

AU - Tang, Sung Chun

AU - Yeh, Shin Joe

AU - Tsai, Li Kai

AU - Kong, Shin

AU - Lien, Li Ming

AU - Chiu, Hou Chang

AU - Chen, Wei Hung

AU - Bai, Chyi Huey

AU - Huang, Tzu Hsuan

AU - Lau, Chi Ieong

AU - Wu, Ya Ying

AU - Yuan, Rey Yue

AU - Hu, Chaur Jong

AU - Sheu, Jau Jiuan

AU - Yu, Jia Ming

AU - Ho, Chun Sum

AU - Chen, Chin I.

AU - Sung, Jia Ying

AU - Weng, Hsing Yu

AU - Han, Yu Hsuan

AU - Huang, Chun Ping

AU - Chung, Wen Ting

AU - Ke, Der Shin

AU - Lin, Huey Juan

AU - Chang, Chia Yu

AU - Yeh, Poh Shiow

AU - Lin, Kao Chang

AU - Cheng, Tain Junn

AU - Chou, Chih Ho

AU - Yang, Chun Ming

AU - Peng, Giia Sheun

AU - Lin, Jiann Chyun

AU - Hsu, Yaw Don

AU - Denq, Jong Chyou

AU - Lee, Jiunn Tay

AU - Hsu, Chang Hung

AU - Lin, Chun Chieh

AU - Yen, Che Hung

AU - Cheng, Chun An

AU - Sung, Yueh Feng

AU - Chen, Yuan Liang

AU - Lien, Ming Tung

AU - Chou, Chung Hsing

AU - Liu, Chia Chen

AU - Yang, Fu Chi

AU - Wu, Yi Chung

AU - Tso, An Chen

AU - Lai, Yu Hua

AU - Chiang, Chun I.

AU - Tsai, Chia Kuang

AU - Liu, Meng Ta

AU - Lin, Ying Che

AU - Hsu, Yu Chuan

AU - Chen, Chih Hung

AU - Sung, Pi Shan

AU - Chern, Chang Ming

AU - Hu, Han Hwa

AU - Wong, Wen Jang

AU - Luk, Yun On

AU - Hsu, Li Chi

AU - Chung, Chih Ping

AU - Tseng, Hung Pin

AU - Liu, Chin Hsiung

AU - Lin, Chun Liang

AU - Lin, Hung Chih

AU - Hu, Chaur Jong

PY - 2012/10/24

Y1 - 2012/10/24

N2 - 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.

AB - 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.

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UR - http://www.scopus.com/inward/citedby.url?scp=84868137461&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0047773

DO - 10.1371/journal.pone.0047773

M3 - Article

C2 - 23112845

SN - 1932-6203

VL - 7

JO - PLoS One

JF - PLoS One

IS - 10

M1 - e47773

ER -

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

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