Zdravkovic Slobodan, Wienke Andreas, Pedersen Nancy L, de Faire Ulf
Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Eur J Hum Genet. 2007 Aug;15(8):872-7. doi: 10.1038/sj.ejhg.5201846. Epub 2007 May 9.
As functional properties of the coronaries may differ between coronary heart disease (CHD) patients with or without angina pectoris (AP), it is possible that different genetic mechanisms could be involved in the various CHD phenotypes. The primary aim of this study was, therefore, to determine the relative importance of genetic factors for AP as well as the impact of AP on CHD death in general. All same-sexed twins born between 1886 and 1958 included in the Swedish Twin Registry served as a base for this study. Information from the Swedish Cause of Death Register was used for diagnosing CHD death. Standard methods applied in twin research such as survival and quantitative genetic models were used. The impact of AP on CHD death was significant among both sexes, with larger estimates for males (hazard ratio and 95% CI 2.0 (1.8-2.3)) than females (1.6 (1.4-1.8)). Probandwise concordances and intraclass correlations for AP and CHD death were in general greater in monozygotic than dizygotic twins among both sexes. Heritability analyses resulted in moderate heritability estimates for AP in both sexes (0.39 (0.29-0.49) for males and 0.43 (0.08-0.51) for females). The correlation between AP and CHD was exclusively explained by the influence of familial factors in both sexes. In conclusion, our data imply genetic influences for AP and CHD death among both sexes and that AP is important as a risk factor for CHD death in both males and females, due in part to shared genetic pathways.
由于冠心病(CHD)患者中有无心绞痛(AP)的冠状动脉功能特性可能不同,因此不同的遗传机制可能参与了各种冠心病表型。因此,本研究的主要目的是确定遗传因素对心绞痛的相对重要性以及心绞痛对总体冠心病死亡的影响。瑞典双胞胎登记处收录的1886年至1958年出生的所有同性双胞胎作为本研究的基础。瑞典死亡原因登记处的信息用于诊断冠心病死亡。采用了双胞胎研究中应用的标准方法,如生存和定量遗传模型。心绞痛对冠心病死亡的影响在两性中均显著,男性的估计值(风险比和95%置信区间2.0(1.8 - 2.3))大于女性(1.6(1.4 - 1.8))。在两性中,单卵双胞胎中心绞痛和冠心病死亡的先证者一致性和组内相关性总体上高于双卵双胞胎。遗传力分析得出两性心绞痛的遗传力估计值适中(男性为0.39(0.29 - 0.49),女性为0.43(0.08 - 0.51))。两性中心绞痛与冠心病之间的相关性完全由家族因素的影响来解释。总之,我们的数据表明两性中心绞痛和冠心病死亡存在遗传影响,并且心绞痛作为冠心病死亡的危险因素在男性和女性中都很重要,部分原因是共享的遗传途径。