HYPERLIPIDEMIA IN CORONARY HEART-DISEASE .2. GENETIC ANALYSIS OF LIPID-LEVELS IN 176 FAMILIES AND DELINEATION OF A NEW INHERITED DISORDER, COMBINED HYPERLIPIDEMIA
HYPERLIPIDEMIA IN CORONARY HEART-DISEASE .2. GENETIC ANALYSIS OF LIPID-LEVELS IN 176 FAMILIES AND DELINEATION OF A NEW INHERITED DISORDER, COMBINED HYPERLIPIDEMIA
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DOI：
10.1172/jci107332
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发表时间：
1973-01-01
影响因子：
15.9
通讯作者：
MOTULSKY, AG
中科院分区：
文献类型：
--
作者：
GOLDSTEIN, JL;SCHROTT, HG;MOTULSKY, AG
为了评估冠心病高脂血症的遗传学，对 176 名心肌梗死幸存者的 2520 名亲属和配偶进行了家庭研究，其中包括 149 名高脂血症患者和 27 名正常血脂患者。亲属中空腹血浆胆固醇和甘油三酯值的分布以及分离分析表明存在五种不同的脂质疾病。其中三种——家族性高胆固醇血症、家族性高甘油三酯血症和家族性混合性高脂血症——似乎代表了三种不同常染色体基因的显性表达，发生在大约 20% 的 60 岁以下幸存者和 7% 的所有老年幸存者中。另外两种疾病——多基因性高胆固醇血症和散发性高甘油三酯血症——分别影响两个年龄组中约 6% 的幸存者。这项研究中确定的最常见的高脂血症遗传形式迄今尚未明确定义，并被指定为家族性混合性高脂血症。受影响的家庭成员的胆固醇和甘油三酯水平均升高。然而，也经常观察到单独增加的胆固醇或增加的甘油三酯水平。该组合性疾病在遗传上与家族性高胆固醇血症和家族性高甘油三酯血症不同，原因如下：（a）先证者亲属中胆固醇和甘油三酯水平的分布模式是独特的； (b) 患有合并性高脂血症的个体的儿童不表现出高胆固醇血症，这与来自患有家族性高胆固醇血症的家庭的高胆固醇血症儿童的发现相反； (c) 对信息交配的分析表明，不同的脂质表型归因于单个常染色体显性基因的可变表达，而不是两个独立基因的分离，例如一个提高胆固醇水平，另一个提高甘油三酯水平。本研究中确定的三个脂质升高基因之一的杂合性在一般人群中的频率可能约为 1%，构成早期诊断的主要问题和预防性治疗。图像
To assess the genetics of hyperlipidemia in coronary heart disease, family studies were carried out in 2520 relatives and spouses of 176 survivors of myocardial infarction, including 149 hyperlipidemic and 27 normolipidemic individuals. The distribution of fasting plasma cholesterol and triglyceride values in relatives, together with segregation analyses, suggested the presence of five distinct lipid disorders. Three of these—familial hypercholesterolemia, familial hypertriglyceridemia, and familial combined hyperlipidemia—appeared to represent dominant expression of three different autosomal genes, occurring in about 20% of survivors below 60 yr of age and 7% of all older survivors. Two other disorders—polygenic hypercholesterolemia and sporadic hypertriglyceridemia—each affected about 6% of survivors in both age groups.The most common genetic form of hyperlipidemia identified in this study has hitherto been poorly defined and has been designated as familial combined hyperlipidemia. Affected family members characteristically had elevated levels of both cholesterol and triglyceride. However, increased cholesterol or increased triglyceride levels alone were also frequently observed. The combined disorder was shown to be genetically distinct from familial hypercholesterolemia and familial hypertriglyceridemia for the following reasons: (a) the distribution pattern of cholesterol and triglyceride levels in relatives of probands was unique; (b) children of individuals with combined hyperlipidemia did not express hypercholesterolemia in contrast to the finding of hypercholesterolemic children from families with familial hypercholesterolemia; and (c) analysis of informative matings suggested that the different lipid phenotypes owed their origin to variable expression of a single autosomal dominant gene and not to segregation of two separate genes, such as one elevating the level of cholesterol and the other elevating the level of triglyceride.Heterozygosity for one of the three lipid-elevating genes identified in this study may have a frequency in the general population of about 1%, constituting a major problem in early diagnosis and preventive therapy.Images