Hassan Mohammed O, Jaju Deepali, Voruganti V Saroja, Bayoumi Riad A, Albarwani Sulayma, Al-Yahyaee Saeed, Aslani Afshin, Snieder Harold, Lopez-Alvarenga Juan C, Al-Anqoudi Zahir M, Alizadeh Behrooz Z, Comuzzie Anthony G
College of Medicine and Health Sciences, Sultan Qaboos University, Sultanate of Oman.
Twin Res Hum Genet. 2011 Jun;14(3):257-67. doi: 10.1375/twin.14.3.257.
We performed a genome-wide scan in a homogeneous Arab population to identify genomic regions linked to blood pressure (BP) and its intermediate phenotypes during mental and physical stress tests.
The Oman Family Study subjects (N = 1277) were recruited from five extended families of ~10 generations. Hemodynamic phenotypes were computed from beat-to-beat BP, electrocardiography and impedance cardiography. Multi-point linkage was performed for resting, mental (word conflict test, WCT) and cold pressor (CPT) stress and their reactivity scores (s), using variance components decomposition-based methods implemented in SOLAR.
Genome-wide scans for BP phenotypes identified quantitative trait loci (QTLs) with significant evidence of linkage on chromosomes 1 and 12 for WCT-linked cardiac output (LOD = 3.1) and systolic BP (LOD = 3.5). Evidence for suggestive linkage for WCT was found on chromosomes 3, 17 and 1 for heart rate (LOD = 2.3), DBP (LOD = 2.4) and left ventricular ejection time (LVET), respectively. For △WCT, suggestive QTLs were detected for CO on chr11 (LOD = 2.5), LVET on chr3 (LOD = 2.0) and EDI on chr9 (LOD = 2.1). For CPT, suggestive QTLs for HR and LVET shared the same region on chr22 (LOD 2.3 and 2.8, respectively) and on chr9 (LOD = 2.3) for SBP, chr7 (LOD = 2.4) for SV and chr19 (LOD = 2.6) for CO. For △CPT, CO and TPR top signals were detected on chr15 and 10 (LOD; 2.40, 2.08) respectively.
Mental stress revealed the largest number of significant and suggestive loci for normal BP reported to date. The study of BP and its intermediate phenotypes under mental and physical stress may help reveal the genes involved in the pathogenesis of essential hypertension.
我们在一个同质化的阿拉伯人群中进行了全基因组扫描，以确定在精神和身体应激测试期间与血压（BP）及其中间表型相关的基因组区域。
阿曼家族研究的受试者（N = 1277）来自五个约10代的大家庭。血流动力学表型由逐搏血压、心电图和阻抗心动图计算得出。使用SOLAR中基于方差成分分解的方法，对静息、精神（单词冲突测试，WCT）和冷加压（CPT）应激及其反应性评分（s）进行多点连锁分析。
对BP表型的全基因组扫描确定了数量性状位点（QTL），在1号和12号染色体上有与WCT相关的心输出量（LOD = 3.1）和收缩压（LOD = 3.5）连锁的显著证据。在3号、17号和1号染色体上分别发现了与WCT相关的心率（LOD = 2.3）、舒张压（LOD = 2.4）和左心室射血时间（LVET）的提示性连锁证据。对于△WCT，在11号染色体上检测到与CO相关的提示性QTL（LOD = 2.5），在3号染色体上检测到与LVET相关的提示性QTL（LOD = 2.0），在9号染色体上检测到与EDI相关的提示性QTL（LOD = 2.1）。对于CPT，与HR和LVET相关的提示性QTL在22号染色体上共享同一区域（LOD分别为2.3和2.8），与SBP相关的提示性QTL在9号染色体上（LOD = 2.3），与SV相关的提示性QTL在7号染色体上（LOD = 2.4），与CO相关的提示性QTL在19号染色体上（LOD = 2.6）。对于△CPT，在15号和10号染色体上分别检测到CO和TPR的最高信号（LOD；2.40，2.08）。
精神应激揭示了迄今为止报道的正常血压的最多显著和提示性位点。对精神和身体应激下的BP及其中间表型的研究可能有助于揭示原发性高血压发病机制中涉及的基因。
