Epistasis analysis for estrogen metabolic and signaling pathway genes on young ischemic stroke patients.
<h4>Background</h4>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-methy...
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2012
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oai:doaj.org-article:d6cc9dd9055d499d8910a6211f1b47e92021-11-18T08:11:10ZEpistasis analysis for estrogen metabolic and signaling pathway genes on young ischemic stroke patients.1932-620310.1371/journal.pone.0047773https://doaj.org/article/d6cc9dd9055d499d8910a6211f1b47e92012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23112845/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.Yi-Chen HsiehJiann-Shing JengHuey-Juan LinChaur-Jong HuChia-Chen YuLi-Ming LienGiia-Sheun PengChin-I ChenSung-Chun TangNai-Fang ChiHung-Pin TsengChang-Ming ChernFang-I HsiehChyi-Huey BaiYi-Rhu ChenHung-Yi ChiouFormosa Stroke Genetic ConsortiumPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 10, p e47773 (2012) |
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Medicine R Science Q Yi-Chen Hsieh Jiann-Shing Jeng Huey-Juan Lin Chaur-Jong Hu Chia-Chen Yu Li-Ming Lien Giia-Sheun Peng Chin-I Chen Sung-Chun Tang Nai-Fang Chi Hung-Pin Tseng Chang-Ming Chern Fang-I Hsieh Chyi-Huey Bai Yi-Rhu Chen Hung-Yi Chiou Formosa Stroke Genetic Consortium Epistasis analysis for estrogen metabolic and signaling pathway genes on young ischemic stroke patients. |
| description |
<h4>Background</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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. |
| format |
article |
| author |
Yi-Chen Hsieh Jiann-Shing Jeng Huey-Juan Lin Chaur-Jong Hu Chia-Chen Yu Li-Ming Lien Giia-Sheun Peng Chin-I Chen Sung-Chun Tang Nai-Fang Chi Hung-Pin Tseng Chang-Ming Chern Fang-I Hsieh Chyi-Huey Bai Yi-Rhu Chen Hung-Yi Chiou Formosa Stroke Genetic Consortium |
| author_facet |
Yi-Chen Hsieh Jiann-Shing Jeng Huey-Juan Lin Chaur-Jong Hu Chia-Chen Yu Li-Ming Lien Giia-Sheun Peng Chin-I Chen Sung-Chun Tang Nai-Fang Chi Hung-Pin Tseng Chang-Ming Chern Fang-I Hsieh Chyi-Huey Bai Yi-Rhu Chen Hung-Yi Chiou Formosa Stroke Genetic Consortium |
| author_sort |
Yi-Chen Hsieh |
| title |
Epistasis analysis for estrogen metabolic and signaling pathway genes on young ischemic stroke patients. |
| title_short |
Epistasis analysis for estrogen metabolic and signaling pathway genes on young ischemic stroke patients. |
| title_full |
Epistasis analysis for estrogen metabolic and signaling pathway genes on young ischemic stroke patients. |
| title_fullStr |
Epistasis analysis for estrogen metabolic and signaling pathway genes on young ischemic stroke patients. |
| title_full_unstemmed |
Epistasis analysis for estrogen metabolic and signaling pathway genes on young ischemic stroke patients. |
| title_sort |
epistasis analysis for estrogen metabolic and signaling pathway genes on young ischemic stroke patients. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/d6cc9dd9055d499d8910a6211f1b47e9 |
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