Family Studies on Hypertension from Probands of Premature Angiographically-proven Coronary Artery Disease

由大規模世代研究及臨床研究結果得 知高血壓是心血管疾病重要的危險因子， 而形成高血壓的機制，除了已知的飲食、 生活習慣因素之外，遺傳因素的影響正是 目前學界的研究重點。國外雙胞胎研究及 家族研究均顯示高血壓有高度的家族聚集 傾向。台灣目前正進行有系統的家族資料 的收集與分析。關於台灣本地生活環境及 種族族群等因素，對於高血壓的影響如 何，實有待進一步釐清。本研究設計經由 已發病的年輕冠狀動脈病人為指標個案收 集家族親屬包括一等級(兄弟姐妹、父母、 子女)，及配偶的血壓值進行高血壓家族聚 集的家族研究。其研究對象是根據台大醫 院心導管診斷為冠狀動脈病人，收集同一 戶家族成員的資料，釐清指標個案與親屬 關係，收集家族成員的血壓及其他相關的 變數資料，利用各種統計模型，首先探討 其家族內高血壓聚集的情形，了解各種親 屬配對的關係，如配偶、親子及手足的關 係研究其相關係數。結果顯示：在收縮壓方面配偶之間的相關係數為-0.27 ，而親子 代之間為0.67 ，在舒張壓方面配偶之間的 相關係數為0.51 ，而親子之間的相關係數 為0.75 。利用複雜分離分析方法探索遺傳 模式。在收縮壓方面，比較各種不同模型 與full model 時以多重基因模型為較佳模 型(χ 2 3=1.7 ，P=0.64)，其中平均值為 125.8 ，變異數為255 ，而配偶之間相關係 數為-0.10 ±0.27 ，親子代之間相關係數為 0.45 ±0.14 ，此值與利用FCOR 軟體算得的 相關係數相近。原因可能是血壓值受到外到環境因素影響以及多重基因互相作用， 本研究並無法確定收縮壓有主要基因效 應。進一步收集不同的樣本以及利用基因 拚圖方式嚐試釐清遺傳及環境之關係是有 其必要，對未來作血壓及血脂的阻介提供 進一步的參考。Introduction: From population-based cohort study and clinical trial data, hypertension was important risk factor for cardiovascular events. The pathogenesis of hypertension was complex, and besides of dietary and life style factors, genetic components have important roles in the pathogenesis of hypertension. There were enough evidences that there was strong familial aggregation of hypertension, and the estimated heritability was around 30-60%, from twin and pedigree studies. We designed the family study, ascertained from probands, to investigate the genetics of blood pressure. Materials and Methods: The patients with coronary artery disease, confirmed by coronary angiography, are identified as probands. The first relationships of proband, including parent-offspring, siblings, and spouse are invited for study. Various anthropometric measurements, including body weight, body height, and blood pressures were collected. Socioeconomic status, physical activity, dietary behavior, smoking and alcohol drinking status were also included as confounders. Familial resemblance and aggregation can be estimated by familial correlation coefficients. By complex segregation analysis of regressive model, we estimated the best mode of inheritance and familial correlation of blood pressure. Results and Discussion: Total 73 patients receiving coronary angiography were recruited into this study. First relatives, including spouse, offspring were invited. The correlation coefficients of systolic blood pressure were –0.27 among spouse pairs, and 0.67 among parent-offspring pairs. The coefficients of body mass index were 0.12 among spouse pairs, and 0.41 among parent-offspring pairs. Compared with arbitrary model, the polygenes model was most fitted model to explain the model of inheritance of systolic blood pressure (χ 2 3=1.7 ，P=0.64), and mean was 125.8 mmHg, variance was 255. The correlation coefficients among spouses were -0.10 ±0.27, those among parent-offspring were 0.45 ±0.14, similar to the results of FCOR. Conclusion: We found significant parent-offspring correlation among blood pressures and body mass index. Polygenes model was the best model to explain the mode of inheritance of systolic blood pressure