GENETIC SUSCEPTIBILITY TO DEATH FROM CORONARY HEART-DISEASE IN A STUDY OF TWINS
GENETIC SUSCEPTIBILITY TO DEATH FROM CORONARY HEART-DISEASE IN A STUDY OF TWINS
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DOI：
10.1056/nejm199404143301503
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发表时间：
1994-04-14
影响因子：
158.5
通讯作者：
DEFAIRE, U
中科院分区：
文献类型：
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作者：
MARENBERG, ME;RISCH, N;DEFAIRE, U
背景。早发冠心病的家族史一直被认为是冠心病的危险因素。利用对1886年至1925年间出生的21,004对瑞典双胞胎26年的随访数据，我们通过评估同卵双胞胎和异卵双胞胎死于冠心病的风险来进一步调查这一问题。研究人群包括3298对同卵双胞胎和5964对异卵双胞胎，以及4012对同卵双胞胎和7730对异卵双胞胎。其中一个双胞胎死于冠心病的年龄被用作预测另一个双胞胎死于冠心病风险的主要独立变量。从1961年和1963年的问卷调查中获得了其他风险因素的信息。使用精算生命表分析来估计冠心病死亡的累积概率。通过多变量生存分析获得相对危险度估计。在男性中，当一个双胞胎在55岁之前死于冠心病时，与另一个双胞胎在55岁之前没有死亡时相比，死于冠心病的相对风险在同卵双胞胎中为8.1(95%置信区间，2.7至24.5)，在异卵双胞胎中为3.8（1.4至10.5）。在这些女性中，当其中一个双胞胎在65岁之前死于冠心病时，同卵双胞胎的相对危险度为15.0(95%置信区间，7.1至31.9)，异卵双胞胎的相对危险度为2.6（1.0至7.1）。在男性和女性中，无论是同卵双胞胎还是异卵双胞胎，随着其中一方死于冠心病的年龄增加，相对危险程度降低。随着年龄的增长，同卵双胞胎的相对危险度估计值与异卵双胞胎的相对危险度估计值的比值接近于1。这些相对危险度受冠心病其他危险因素的影响较小。我们的研究结果表明，在年轻时，女性和男性的冠心病死亡都受到遗传因素的影响。研究结果还表明，遗传效应随着年龄的增长而减弱。
Background. A family history of premature coronary heart disease has long been thought to be a risk factor for coronary heart disease. Using data from 26 years of follow-up of 21,004 Swedish twins born between 1886 and 1925, we investigated this issue further by assessing the risk of death from coronary heart disease in pairs of monozygotic and dizygotic twins.Methods. The study population consisted of 3298 monozygotic and 5964 dizygotic male twins and 4012 monozygotic and 7730 dizygotic female twins. The age at which one twin died of coronary heart disease was used as the primary independent variable to predict the risk of death from coronary heart disease in the other twin. Information about other risk factors was obtained from questionnaires administered in 1961 and 1963. Actuarial life-table analysis was used to estimate the cumulative probability of death from coronary heart disease. Relative-hazard estimates were obtained from a multivariate survival analysis.Results. Among the men, the relative hazard of death from coronary heart disease when one's twin died of coronary heart disease before the age of 55 years, as compared with the hazard when one's twin did not die before 55, was 8.1 (95 percent confidence interval, 2.7 to 24.5) for monozygotic twins and 3.8 (1.4 to 10.5) for dizygotic twins. Among the women, when one's twin died of coronary heart disease before the age of 65 years, the relative hazard was 15.0 (95 percent confidence interval, 7.1 to 31.9) for monozygotic twins and 2.6 (1.0 to 7.1) for dizygotic twins. Among both the men and the women, whether monozygotic or dizygotic twins, the magnitude of the relative hazard decreased as the age at which one's twin died of coronary heart disease increased. The ratio of the relative-hazard estimate for the monozygotic twins to the estimate for the dizygotic twins approached 1 with increasing age. These relative hazards were little influenced by other risk factors for coronary heart disease.Conclusions. Our findings suggest that at younger ages, death from coronary heart disease is influenced by genetic factors in both women and men. The results also imply that the genetic effect decreases at older ages.