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The Polymorphism in ADORA3 Decreases Transcriptional Activity and Influences the Chronic Heart Failure Risk in the Chinese

AIM: To investigate the genetic contribution of adenosine A3 receptor (ADORA3) gene polymorphisms in the pathogenesis of chronic heart failure (CHF). METHODS: Firstly, a case-control study was performed to investigate the association of ADORA3 polymorphisms with CHF risk. Three hundred northern Chin...

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Autores principales: He, Hai-Rong, Li, Yuan-Jie, He, Gong-Hao, Qiang, Hua, Zhai, Ya-Jing, Ma, Mao, Wang, Ya-Jun, Wang, Yan, Zheng, Xiao-Wei, Dong, Ya-Lin, Lyu, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6000890/
https://www.ncbi.nlm.nih.gov/pubmed/29955603
http://dx.doi.org/10.1155/2018/4969385
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author He, Hai-Rong
Li, Yuan-Jie
He, Gong-Hao
Qiang, Hua
Zhai, Ya-Jing
Ma, Mao
Wang, Ya-Jun
Wang, Yan
Zheng, Xiao-Wei
Dong, Ya-Lin
Lyu, Jun
author_facet He, Hai-Rong
Li, Yuan-Jie
He, Gong-Hao
Qiang, Hua
Zhai, Ya-Jing
Ma, Mao
Wang, Ya-Jun
Wang, Yan
Zheng, Xiao-Wei
Dong, Ya-Lin
Lyu, Jun
author_sort He, Hai-Rong
collection PubMed
description AIM: To investigate the genetic contribution of adenosine A3 receptor (ADORA3) gene polymorphisms in the pathogenesis of chronic heart failure (CHF). METHODS: Firstly, a case-control study was performed to investigate the association of ADORA3 polymorphisms with CHF risk. Three hundred northern Chinese Han CHF patients and 400 ethnicity-matched healthy controls were included. Four polymorphisms were genotyped. This case-control study was also replicated in 304 CHF patients and 402 controls from southern China. Finally, the functional variability of positive polymorphism was analyzed using luciferase reporter assay and real-time PCR. RESULTS: Overall, the rs1544223 was significantly associated with CHF risk under the dominant model (P = 0.046, OR = 1.662, 95% CI = 1.009–2.738). But it did not affect disease severity. These results were also consistent in replicated population. In addition, the transcriptional activity for promoter with the A allele was lower than that with the G allele (n = 3, 4.501 ± 0.308 versus 0.571 ± 0.114, P < 0.01) and ADORA3 mRNA levels were significantly higher in GG homozygotes than subjects carrying GA (n = 6, 0.058 ± 0.01 versus 0.143 ± 0.068, P = 0.004) or AA genotypes (n = 6, 0.065 ± 0.01 versus 0.143 ± 0.068, P = 0.008). CONCLUSIONS: Should the findings be validated by further studies with larger patient samples and in different ethnicities, they may provide novel insight into the pathogenesis of CHF.
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spelling pubmed-60008902018-06-28 The Polymorphism in ADORA3 Decreases Transcriptional Activity and Influences the Chronic Heart Failure Risk in the Chinese He, Hai-Rong Li, Yuan-Jie He, Gong-Hao Qiang, Hua Zhai, Ya-Jing Ma, Mao Wang, Ya-Jun Wang, Yan Zheng, Xiao-Wei Dong, Ya-Lin Lyu, Jun Biomed Res Int Research Article AIM: To investigate the genetic contribution of adenosine A3 receptor (ADORA3) gene polymorphisms in the pathogenesis of chronic heart failure (CHF). METHODS: Firstly, a case-control study was performed to investigate the association of ADORA3 polymorphisms with CHF risk. Three hundred northern Chinese Han CHF patients and 400 ethnicity-matched healthy controls were included. Four polymorphisms were genotyped. This case-control study was also replicated in 304 CHF patients and 402 controls from southern China. Finally, the functional variability of positive polymorphism was analyzed using luciferase reporter assay and real-time PCR. RESULTS: Overall, the rs1544223 was significantly associated with CHF risk under the dominant model (P = 0.046, OR = 1.662, 95% CI = 1.009–2.738). But it did not affect disease severity. These results were also consistent in replicated population. In addition, the transcriptional activity for promoter with the A allele was lower than that with the G allele (n = 3, 4.501 ± 0.308 versus 0.571 ± 0.114, P < 0.01) and ADORA3 mRNA levels were significantly higher in GG homozygotes than subjects carrying GA (n = 6, 0.058 ± 0.01 versus 0.143 ± 0.068, P = 0.004) or AA genotypes (n = 6, 0.065 ± 0.01 versus 0.143 ± 0.068, P = 0.008). CONCLUSIONS: Should the findings be validated by further studies with larger patient samples and in different ethnicities, they may provide novel insight into the pathogenesis of CHF. Hindawi 2018-05-31 /pmc/articles/PMC6000890/ /pubmed/29955603 http://dx.doi.org/10.1155/2018/4969385 Text en Copyright © 2018 Hai-Rong He et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
He, Hai-Rong
Li, Yuan-Jie
He, Gong-Hao
Qiang, Hua
Zhai, Ya-Jing
Ma, Mao
Wang, Ya-Jun
Wang, Yan
Zheng, Xiao-Wei
Dong, Ya-Lin
Lyu, Jun
The Polymorphism in ADORA3 Decreases Transcriptional Activity and Influences the Chronic Heart Failure Risk in the Chinese
title The Polymorphism in ADORA3 Decreases Transcriptional Activity and Influences the Chronic Heart Failure Risk in the Chinese
title_full The Polymorphism in ADORA3 Decreases Transcriptional Activity and Influences the Chronic Heart Failure Risk in the Chinese
title_fullStr The Polymorphism in ADORA3 Decreases Transcriptional Activity and Influences the Chronic Heart Failure Risk in the Chinese
title_full_unstemmed The Polymorphism in ADORA3 Decreases Transcriptional Activity and Influences the Chronic Heart Failure Risk in the Chinese
title_short The Polymorphism in ADORA3 Decreases Transcriptional Activity and Influences the Chronic Heart Failure Risk in the Chinese
title_sort polymorphism in adora3 decreases transcriptional activity and influences the chronic heart failure risk in the chinese
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6000890/
https://www.ncbi.nlm.nih.gov/pubmed/29955603
http://dx.doi.org/10.1155/2018/4969385
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