首页> 外文期刊>Journal of hypertension >New polymorphisms of the angiotensin II type 1 receptor gene and their associations with myocardial infarction and blood pressure: the ECTIM study. Etude Cas-Temoin de l'Infarctus du Myocarde.
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New polymorphisms of the angiotensin II type 1 receptor gene and their associations with myocardial infarction and blood pressure: the ECTIM study. Etude Cas-Temoin de l'Infarctus du Myocarde.

机译:ECTIM研究:血管紧张素II 1型受体基因的新多态性及其与心肌梗塞和血压的关系。练习曲《心肌梗塞练习曲》(Etude Cas-Temoin de l'Infarctus du Myocarde)。

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OBJECTIVE: In an earlier report, we suggested that a polymorphism located in the 3' untranslated region of the angiotensin II type 1 receptor gene (AT1R+1166 A/C) might interact with the angiotensin I converting enzyme (ACE) insertion/deletion (I/D) polymorphism to increase the risk of myocardial infarction. Since the AT1R+1166 A/C polymorphism does not appear to be functional, we postulated that it might be in linkage disequilibrium with an unidentified functional variant which would affect the regulation of the gene in response to angiotensin II. The present study was conducted to identify new polymorphisms of the AT1R gene that might be responsible for this interaction. METHODS: The first four exons, which are untranslated, and 2.2 kb in the 5' flanking region of the AT1R gene were explored by polymerase chain reaction/single-strand conformation polymorphism. Seven polymorphisms were detected in the 5' region at positions -1424, -810, -713, -521, -214, -213 and -153 upstream from the start of transcription. The genotypes of the -810, -713, -214, -213 and -153 polymorphisms were completely concordant. One substitution was detected at the 55th nucleotide of exon 4. These polymorphisms, together with the +1166 A/C polymorphism and a previously described T/C substitution at the 573th nucleotide of exon 5, were genotyped in the Etude Cas-Temoin de l'Infarctus du Myocarde (ECTIM) study, a multicentre study comparing 651 patients who had survived a myocardial infarction and 728 controls from Belfast (United Kingdom) and Lille, Strasbourg and Toulouse (France). RESULTS: The newly identified polymorphisms were not in linkage disequilibrium with the +1166 A/C polymorphism and therefore could not explain the interaction observed with ACE I/D. None of the polymorphisms was associated with blood pressure levels in control subjects. In the four populations, the A allele of the -810 polymorphism was associated with a lower risk of myocardial infarction (population-adjusted odds ratio of 0.80, confidence interval 0.65-0.97, P< 0.05). CONCLUSIONS: None of the newly identified polymorphisms could account for the previously described interaction between the AT1R+1166 A/C and the ACE I/D polymorphisms affecting the risk of myocardial infarction. However, the present study suggests that AT1R-810 T/A, or other polymorphisms which are in complete association with it, might be associated with the risk of myocardial infarction. Further studies are required to confirm this finding and to identify the functional variants.
机译:目的:在较早的报告中,我们建议位于血管紧张素II 1型受体基因(AT1R + 1166 A / C)3'非翻译区的多态性可能与血管紧张素I转化酶(ACE)的插入/缺失相互作用( I / D)多态性会增加心肌梗塞的风险。由于AT1R + 1166 A / C多态性似乎不起作用,因此我们推测它可能与未知的功能性变体连锁不平衡,这会影响对血管紧张素II的基因调控。进行本研究以鉴定可能导致这种相互作用的AT1R基因的新多态性。方法:采用聚合酶链反应/单链构象多态性研究AT1R基因5'侧翼区域中未翻译的前四个外显子和2.2 kb。从转录开始上游在-1424,-810,-713,-521,-214,-213和-153位置的5'区域检测到7个多态性。 -810,-713,-214,-213和-153多态性的基因型完全一致。在外显子4的第55个核苷酸处检测到一个取代。这些多态性与+1166 A / C多态性以及先前描述的外显子5的573个核苷酸处的T / C取代一起在Etude Cas-Temoin de l基因型中进行了分型。 '心肌梗塞(ECTIM)研究是一项多中心研究,比较了来自贝尔法斯特(英国)和里尔,斯特拉斯堡和图卢兹(法国)的651例心肌梗死幸存者和728名对照。结果:新发现的多态性与+1166 A / C多态性没有连锁不平衡,因此不能解释与ACE I / D的相互作用。没有一个多态性与对照组的血压水平有关。在这四个人群中,-810基因多态性的A等位基因与较低的心肌梗死风险相关(人群校正后的优势比为0.80,置信区间为0.65-0.97,P <0.05)。结论:新发现的多态性都不能解释先前描述的AT1R + 1166 A / C和ACE I / D多态性之间影响心肌梗塞风险的相互作用。但是,本研究表明AT1R-810 T / A或与其完全相关的其他多态性可能与心肌梗死的风险有关。需要进一步的研究以确认这一发现并确定功能变异。

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