The Polymorphism in ADORA3 Decreases Transcriptional Activity and Influences the Chronic Heart Failure Risk in the Chinese.
The Polymorphism in ADORA3 Decreases Transcriptional Activity and Influences the Chronic Heart Failure Risk in the Chinese.
复制标题
DOI：
10.1155/2018/4969385
复制
发表时间：
2018
影响因子：
--
通讯作者：
Lyu J
中科院分区：
文献类型：
--
作者：
He HR;Li YJ;He GH;Qiang H;Zhai YJ;Ma M;Wang YJ;Wang Y;Zheng XW;Dong YL;Lyu J
探讨腺苷A3受体（ADORA 3）基因多态性在慢性心力衰竭（CHF）发病中的作用。 首先，我们进行了一项病例对照研究，以探讨ADORA 3基因多态性与CHF风险的关系。纳入300例北方汉族CHF患者和400例种族匹配的健康对照。四个多态性基因分型。该病例对照研究也在中国南方的304例CHF患者和402例对照中重复。最后，采用荧光素酶报告基因分析和实时荧光定量PCR分析阳性多态性的功能变异性。 总体而言，rs 1544223在显性模型下与CHF风险显著相关（P = 0.046，OR = 1.662，95%CI = 1.009-2.738）。但这并不影响疾病的严重程度。这些结果在重复群体中也是一致的。此外，A等位基因启动子的转录活性低于G等位基因启动子GG纯合子的ADORA 3 mRNA水平显著高于GA携带者（n = 3，4.501 ± 0.308vs0.571 ± 0.114，P < 0.01 AA基因型（n = 6，0.065 ± 0.01对0.143 ± 0.068，P = 0.008）。 如果这些发现通过更大样本和不同种族的进一步研究得到验证，它们可能为CHF的发病机制提供新的见解。
To investigate the genetic contribution of adenosine A3 receptor (ADORA3) gene polymorphisms in the pathogenesis of chronic heart failure (CHF). 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. 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). 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.
登录
查看更多内容
影响因子：
6.2
作者：
Campbell NG;Zhu CB;Lindler KM;Yaspan BL;Kistner-Griffin E;NIH ARRA Consortium;Hewlett WA;Tate CG;Blakely RD;Sutcliffe JS
通讯作者：
Sutcliffe JS
影响因子：
20.1
作者：
Black, RG;Guo, YR;Auchampach, JA
通讯作者：
Auchampach, JA
人组胺受体H4基因多态性与中国汉族乳腺癌的相关性
影响因子：
3.5
作者：
He, Gong-Hao;Lu, Jun;Xu, Gui-Li
通讯作者：
Xu, Gui-Li
DOI：
10.1152/ajpheart.1997.273.3.h1324
发表时间：
1997-09-01
影响因子：
4.8
作者：
Maldonado, C;Qiu, YM;Bolli, R
通讯作者：
Bolli, R
影响因子：
10.8
作者：
Mallet, RT;Lee, SC;Downey, HF
通讯作者：
Downey, HF