SEGREGATION ANALYSIS OF APOLIPOPROTEINS A1 AND B IN FAMILIES OF HIGH RISK AND CONTROL ADOLESCENTS
Date Issued
2000
Date
2000
Author(s)
CHIEN, KUO-LIONG
Abstract
背景與目標：脂蛋白元A1 (Apo A1) 與B (Apo B) 是預測心血管疾病發生的重要因子。家族及雙胞胎研究證實Apo A1及Apo B有明顯的遺傳性，然而之前關於兩者的分離分析研究，或者樣本來源異質性高，或是指標個案均是已發病的成年人，因此造成一些歧異的結論。本研究之目標在於由同一社區選取青少年指標個案及其家屬，以探討Apo A1及B的遺傳模式。
方法：高危險組的指標個案來自某一國中學生中有較高危險分數者，而控制組的指標個案則來自其餘學生中隨機取樣；指標個案的一等親家族成員也納入研究。利用多變數線性模型調整Apo A1及Apo B的值，進一步利用家族相關係數，混合分析及複雜分離分析方法來決定Apo A1及B在家族成員中的遺傳模式。
結果：控制Apo A1濃度的最佳解釋模型是環境因素加上多重基因效應，其中配偶之間有明顯相關，而高危險組及控制組之間並沒有明顯的異質性。若依個別家族支持模型的程度來分，支持環境模型的家族中有較高的三酸甘油酯及Apo B濃度。控制Apo B濃度的最佳解釋模型則是主效基因加上多重基因效應模型，而支持主效基因效應模型的家族中有較高的三酸甘油酯及Apo B濃度。
結論：以青少年人為指標個案的分離分析研究，顯示Apo A1及Apo B有不同的遺傳模型，因而兩者可能有不同的控制因子，其中Apo B較具有主要基因的可能。
Background and Objectives: Apolipoprotein (Apo) A1 and B concentrations are good discriminators for morbidity and mortality of cardiovascular diseases. There is significant heritability estimate of Apo A1 and B in family and twin studies. Reports of segregation analyses on the mode of inheritance of Apo A1 and B are inconsistent because of heterogeneity in study population or adult diseased probands. The objectives of this study were to study the mode of inheritance of Apo A1 and B in the families of high risk and control adolescents, ascertained from the same community.
Methods: High risk probands were ascertained according to higher risk scores in one school students, and control probands were selected by randomization in other students. First relatives were recruited. Apo A1 and Apo B were measured by turbidmetric immunoassay methods. After adjusted for gender, age, body mass index, smoking and drinking status, residual values were subjects to further analyses including familial correlation, commingling analysis and complex segregation analysis.
Results: The mode of inheritance of Apo A1 was best explained by nontransmitted environmental plus familial correlation model, and there were significant spouse correlation. No heterogeneity existed between high risk and control families. There were higher levels of triglyceride and Apo B values in families supporting environmental model than in families supporting Mendel model. The mode of inheritance of Apo B was best explained by major gene plus familial correlation model. Higher triglyceride and Apo B levels were found in families supporting Mendel model.
Conclusions: There are different modes of inheritance of Apo A1 and Apo B in familes of adolescent probands. Major gene effect is demonstrated in controlling Apo B level, and further identification of this gene locus will be studied.
Subjects
複雜分離分析
脂蛋白元 A1
脂蛋白元 B
遺傳流行病學
complex segregation analysis
apolipoprotein A1
apolipoprotein B
genetic epidemiology
Type
thesis