意大利人群中肾素-血管紧张素-醛固酮系统的基因多态性与动脉高血压：GENIPER项目
Genetic polymorphism of the renin-angiotensin-aldosterone system and arterial hypertension in the Italian population: the GENIPER Project.
作者信息
Castellano Maurizio, Glorioso Nicola, Cusi Daniele, Sarzani Riccardo, Fabris Bruno, Opocher Giuseppe, Zoccali Carmine, Golin Raffaello, Veglio Franco, Volpe Massimo, Mantero Franco, Fallo Francesco, Rossi Gian Paolo, Barlassina Cristina, Tizzoni Laura, Filigheddu Fabiana, Giacchè Mara, Rossi Federica
机构信息
Dipartimento di Scienze Mediche e Chirurgiche, University of Brescia, c/o 2Medicina, Spedali Civili, 25100 Brescia, Italy.
出版信息
J Hypertens. 2003 Oct;21(10):1853-60. doi: 10.1097/00004872-200310000-00012.
OBJECTIVE
To detect the association of single polymorphisms of the renin-angiotensin-aldosterone system (RAAS), or different combinations thereof, with hypertension.
DESIGN AND METHODS
The GENIPER database is the result of a collaborative effort of 13 Italian research centres to collect genomic DNA in subjects well characterized in terms of blood pressure status. A total of 2461 subjects (normotensive = 611; hypertensive = 1850) were selected and genotyped for the angiotensin-converting enzyme insertion/deletion (ACE I/D), angiotensinogen (AGT) T/C704, angiotensin receptor type 1 (AT1) A/C1166 and aldosterone synthase (ALDO) T/C-344 genetic variants.
RESULTS
Allele frequencies were homogeneous over the Italian territory, with the relevant exception of the ACE I/D, the D allele being significantly less frequent in the northern region (61%) than in the rest of the country (67%; P < 0.0001). When comparing allele and genotype distributions in normotensives and hypertensives, the latter presented a small but statistically significant increase of the C allele of AGT T/C704, the A allele of AT1 A/C1166 and the T allele of ALDO T/C-344 polymorphisms (P = 0.018, P = 0.037 and P = 0.015, respectively), with similar trends all over the country. A step-wise logistic regression analysis confirmed these findings, by entering in the model as independent predictors of blood pressure status of AGT T/C704 (P = 0.013), ALDO T/C-344 (P = 0.032) and AT1 A/C1166 polymorphisms (P = 0.075), but not ACE I/D (P = 0.996). We also found some evidence of an additive effect of individual genetic variants of the RAAS, modulating at different levels the same functional pathway, on the risk of developing hypertension, but no synergistic interaction was observed.
CONCLUSIONS
Our results suggest that some allelic variants of RAAS genes carry a small but identifiable risk of developing arterial hypertension.
目的
检测肾素 - 血管紧张素 - 醛固酮系统（RAAS）的单核苷酸多态性或其不同组合与高血压的关联。
设计与方法
GENIPER数据库是13个意大利研究中心共同努力的成果，旨在收集血压状况特征明确的受试者的基因组DNA。共选取了2461名受试者（血压正常者 = 611名；高血压患者 = 1850名），并对其进行血管紧张素转换酶插入/缺失（ACE I/D）、血管紧张素原（AGT）T/C704、血管紧张素1型受体（AT1）A/C1166和醛固酮合酶（ALDO）T/C - 344基因变异的基因分型。
结果
等位基因频率在意大利境内较为均匀，但ACE I/D基因是个例外，D等位基因在北部地区的频率（61%）显著低于该国其他地区（67%；P < 0.0001）。在比较血压正常者和高血压患者的等位基因及基因型分布时，高血压患者中AGT T/C704的C等位基因、AT1 A/C1166的A等位基因和ALDO T/C - 344多态性的T等位基因出现了虽小但具有统计学意义的增加（分别为P = 0.018、P = 0.037和P = 0.015），且在全国范围内趋势相似。逐步逻辑回归分析证实了这些发现，将AGT T/C704（P = 0.0）、ALDO T/C - 344（P = 0.032）和AT1 A/C1166多态性（P = 0.075）作为血压状况的独立预测因子纳入模型，但ACE I/D未纳入（P = 0.996）。我们还发现了一些证据，表明RAAS的个体基因变异具有累加效应，在不同水平上调节相同的功能途径，从而影响患高血压的风险，但未观察到协同相互作用。
结论
我们的结果表明，RAAS基因的某些等位基因变异携带了患动脉高血压的小但可识别的风险。
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