Evidence, from combined segregation and linkage analysis, that a variant of the angiotensin I-converting enzyme (ACE) gene controls plasma ACE levels.
Evidence, from combined segregation and linkage analysis, that a variant of the angiotensin I-converting enzyme (ACE) gene controls plasma ACE levels.
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发表时间：
1992-07
影响因子：
9.8
通讯作者：
L. Tiret;B. Rigat;S. Visvikis;C. Breda;P. Corvol;F. Cambien;F. Soubrier
中科院分区：
文献类型：
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作者：
L. Tiret;B. Rigat;S. Visvikis;C. Breda;P. Corvol;F. Cambien;F. Soubrier
分离分析和ACE基因插入/缺失（I/D）多态性的鉴定均表明血浆血管紧张素I转换酶（ACE）水平的遗传控制假说，该多态性对ACE水平的变异性有很大贡献。为了阐明I/D多态性是否直接参与遗传调控，对98个健康核心家系的血浆ACE活性和I/D多态性基因型进行了检测。ACE水平的家族相关性模式与配偶之间的零相关性以及同等的父母-子女和同胞-同胞相关性（0.24 +/-0.04）相一致。分离分析表明，这种家族相似性可以完全解释为一个共显性主基因的传递。I/D多态性与ACE水平的显著差异相关，尽管这些差异不如分离分析中观察到的那些明显。校正多态性效应后，剩余遗传力（0.280 +/-0.096）是显著的。最后，结合分离和连锁分析提供的证据表明，主基因效应是由于ACE基因的变体，在强烈的连锁不平衡与I/D多态性。标记等位基因I似乎总是与以较低ACE水平为特征的主基因等位基因相关。等位基因I的频率为.431 +/- .025，主要等位基因s的频率为.557 +/- .041。主基因的共显性效应等于1.3个残差标准差，占ACE水平总变异的44%，而I/D多态性占28%。（250字处删节）
The hypothesis of a genetic control of plasma angiotensin I-converting enzyme (ACE) level has been suggested both by segregation analysis and by the identification of an insertion/deletion (I/D) polymorphism of the ACE gene, a polymorphism contributing much to the variability of ACE level. To elucidate whether the I/D polymorphism was directly involved in the genetic regulation, plasma ACE activity and genotype for the I/D polymorphism were both measured in a sample of 98 healthy nuclear families. The pattern of familial correlations of ACE level was compatible with a zero correlation between spouses and equal parent-offspring and sib-sib correlations (.24 +/- .04). A segregation analysis indicated that this familial resemblance could be entirely explained by the transmission of a codominant major gene. The I/D polymorphism was associated with marked differences of ACE levels, although these differences were less pronounced than those observed in the segregation analysis. After adjustment for the polymorphism effects, the residual heritability (.280 +/- .096) was significant. Finally, a combined segregation and linkage analysis provided evidence that the major-gene effect was due to a variant of the ACE gene, in strong linkage disequilibrium with the I/D polymorphism. The marker allele I appeared always associated with the major-gene allele s characterized by lower ACE levels. The frequency of allele I was .431 +/- .025, and that of major allele s was .557 +/- .041. The major gene had codominant effects equal to 1.3 residual SDs and accounted for 44% of the total variability of ACE level, as compared with 28% for the I/D polymorphism.(ABSTRACT TRUNCATED AT 250 WORDS)