GENETIC ANALYSIS OF HYPERTENSION IN GHANA

与欧洲裔美国人相比，高血压影响非裔美国人的比例不成比例。有人认为，这是由于遗传易感性导致美国的表型差异加剧。此外，众所周知，黑人的高血压治疗与白人不同。因此，为了更好地诊断和治疗受影响的个体，了解非洲裔美国人这种疾病的潜在遗传学是很重要的。由于原发性高血压的病因复杂，因此有必要简化对该病的任何研究，以最大限度地发现易感基因。我将通过研究西非个体的疾病来做到这一点。有两个因素使这种策略更有可能成功。首先，西非人在基因上比非洲裔非洲人更同质；非洲裔美国人的基因组大约有30%是欧洲人。因此，在美国，许多基因分析将无法检测出即使是中等影响的基因，因为不同的易感基因可能存在于整个非洲裔美国人身上，甚至可能存在于同一个家庭中。这将使检测这些基因变得困难甚至不可能。其次，这种疾病在非洲很少见，这使得那些高血压患者更有可能有遗传易感性。拟议的研究将招募来自加纳的个体来研究几种基因与原发性高血压的关系。两个研究领域将分别采用两种方法。首先，将从阿克拉和农村的高血压和正常个体中随机收集人口样本。这种关联将用于比较整个基因组中标记个体的等位基因频率和基因型频率。农村人口尤其重要，因为非洲农村的高血压发病率一般低于10%，在这种环境下患病的人最有可能具有最强的遗传易感性。

Hypertension affects a disproportionate number of African-Americans as compared to European Americans. It has been suggested that this is due to a genetic predisposition that causes accentuated phenotypic differences in the US. In addition, it is well known that treatment of hypertension in Blacks is different from that in Whites. It is therefore important to understand the underlying genetics of this disease in African-Americans in order to better diagnose and treat affected individuals. Since the etiology of essential hypertension is complex, it is necessary to simplify any study of this disease to maximize the possibly of finding predisposing genes. I will do this by studying the disease in individuals from West Africa. Two things make this strategy more likely to succeed. First, West Africans are genetically more homogeneous than African-Africans; the African-American genome is approximately 30% European. Therefore, in the US many genetic analyses will be unable to detect genes with even a moderate effect because different predisposing genes may be present in the African-Americans as a whole and perhaps even the same family. This will make the detection of any of these genes difficult to impossible. Second, the disease is rarer in Africa,, making those individuals who are hypertensive more likely to have a genetic predisposition. The proposed study will recruit individuals from Ghana to study the association of several genes with essential hypertension. Two approaches will be taken in each of two study areas. First, random population samples will be collected from both hypertensive and normotensive individuals in Accra and rural villages. This association will be used to compare allele frequencies and genotype frequencies from individuals in the markers throughout the genome. The rural populations will be especially important as the incidence of hypertension in rural Africa is generally below 10% and individuals who have the disease in this environment are most likely to short the strongest genetic predisposition.