成年人高密度脂蛋白膽固醇濃度的家族相關與分離分析研究: 以健檢病人為指標個案之家族遺傳研究設計

Abstract

由大規模世代研究及臨床研究結果得知血脂異常 是心血管疾病重要的危險因子，而其中以高密度脂蛋 白膽固醇(HDL-C)是重要的保護因子，國外雙胞胎研究 及家族研究均顯示血脂異常有高度的家族聚集傾向。 本研究設計經由三級醫院健檢其一等親家人作為研究 對象，收集家族親屬包括一等親(兄弟姐妹、父母)血脂 肪值進行HDL-C 濃度的家族研究。自1998 年8 月開 始到1999 年9 月收集總共1313 位樣本，其中包括有 530 對配偶關係，76 對親子及以52 對手足之間的配 對。結果顯示：各種血脂質如cholesterol 、triglyceride 、 HDL-C 及LDL-C 值，均可看到在親子之間的相關係數 均是很高，而且以HDL-C 的r=0.436 最高。在手足之 間的相關係數則是以HDL-C 最高，高達0.505 。混合 分析結果顯示，以3 個成份的混合分析可以最佳解釋 模型，因此我們認為HDL-C 的分佈由3 個成份的混合 模型為最佳模型。其中標準化平均值分別為-0.346 、 0.833 、4.370 ，而變異數為0.516 、1.043 及0.085 ，而 分別所作的比率為71.5%、28.2% 及0.3%。進一步在 分離分析時發現隱性基因為一較好的模型。我們確實 可以發現有一隱性基因作用在HDL-c 濃度的控制。其中其基因頻率為0.280 ，三個平均值為 79.5 ，50.5 及50.5 mg/dL ，而族群變異數為127.1 。配偶之間的相關係數為0.285 ，而子代之間的相關係數為0.466 ，估計其遺傳率為62.7%。因此，我們結論：在以醫院健檢 的病人之家族成員中，HDL-C 有明顯的遺傳因素存在，而且是一隱性基因的作用。

Introduction: There were enough evidences that there was strong familial aggregation of HDL-C concentration in Caucasian, and the estimated heritability was around 20-40% from twin and pedigree studies. But there were insufficient evidences of genetic components among adult Chinese. Materials and Methods: We collected 1,313 subjects, including 530 spouse, 76 parent-offspring and 52 sibling pairs from Aug, 1998 to Sep, 1999. HDL-C was measured following precipitation of apolipoprotein B-containing lipoproteins with phosphotungstic acid and magnesium ions (Boehringer Mannheim, Germany). Residual HDL-C levels, adjusted after age and gender, are used to further genetic analysis, including familial correlation, commingling analysis, and complex segregation analysis. Results and Conclusion: There are significantly high correlation coefficients in parent-offspring and sibling pairs in HDL concentration (0.436 and 0.505, respectively). Commingling analyses demonstrated that three-component distribution was the best-fit model to explain the variation of HDL, with standardized mean values with -0.346, 0.833, 4.370; with proportions of 71.5%, 28.2% and 0.3%. Complex segregation analyses clearly showed that the mode of inheritance of HDL-C was controlled by one recessive major gene effect, with gene frequency of 0.280, and three means of 79.5, 50.5 and 50.5 mg/dL. The variance was 127.1, and correlation coefficients in spouse and siblings were 0.285 and 0.466, respectively, and the estimated heritability was 62.7%. So we concluded that in the population based on hospital health examination, there are significant genetic components in HDL-C, and one recessive major gene effect could be clearly demonstrated.