遗传和环境因素对双胞胎人群腹主动脉瘤发展的影响。
Genetic and environmental contributions to abdominal aortic aneurysm development in a twin population.
机构信息
Department of Vascular Surgery, Karolinska University Hospital, Stockholm, Sweden.
出版信息
J Vasc Surg. 2010 Jan;51(1):3-7; discussion 7. doi: 10.1016/j.jvs.2009.08.036. Epub 2009 Nov 24.
BACKGROUND
The contribution of hereditary and environmental factors to the development of abdominal aortic aneurysms (AAAs) is still partly unknown. The aim of this study was to analyze the role of these factors in a large population-based sample of twins.
METHODS
The Swedish Twin Registry, containing data on twins born in the country since 1886, was cross-linked with the Inpatient Registry, providing national coverage of discharge diagnoses coded according to the International Classification of Diseases (ICD). All twins with an infrarenal AAA were identified. Concordance rates and tetrachoric correlations were calculated for monozygotic (MZ) and dizygotic (DZ) twins. Tetrachoric correlations were calculated assuming an underlying normal distribution of liability, with multiple factors contributing additively and a threshold value that discriminates between AAA and no AAA. Higher concordance rates and correlations of liability in MZ twins than in DZ twins suggest that genetic factors influence disease development. Structural equation modeling techniques, Mx-analyses, were used to estimate the contributions of genetic effects as well as shared and nonshared environmental factors for development of AAA.
RESULTS
There were 172,890 twins registered at the time of the study including 265 twins (81% men; mean age 72 years; range, 48-94) with AAA. There were 7 MZ and 5 DZ concordant pairs as well as 44 MZ and 197 DZ discordant pairs with AAA. The probandwise concordance rates for MZ and DZ pairs were 24% and 4.8%, respectively. The tetrachoric correlations were 0.71 in MZ pairs and 0.31 in DZ pairs. The odds ratio (OR) was 71 (95% confidence interval [CI] 27-183) for MZ twins and 7.6 (95% CI 3.0-19) for DZ twins. In the structural equation models, genetic effects accounted for 70% (95% CI 0.33-0.83), shared environmental effects for 0% (95% CI 0-0.27), and nonshared environmental effects for 30% (95% CI 0.17-0.46) of the phenotypic variance among twins.
CONCLUSION
These data provide robust epidemiologic evidence that heritability contributes to aneurysm formation. Concordances and correlations were higher in MZ compared with DZ twins, indicating genetic effects. There was a 24% probability that an MZ twin of a person with AAA will have the disease. The twin of an MZ twin with AAA had a risk of AAA that was 71 times that of the MZ twin of a person without AAA. A heritability of 70% of the total trait variance was estimated. The remaining variance was explained by nonshared environmental factors with no support for a role of shared environmental influences.
背景
遗传和环境因素对腹主动脉瘤（AAA）发展的贡献仍部分未知。本研究旨在分析这些因素在大型基于人群的双胞胎样本中的作用。
方法
瑞典双胞胎登记处包含了自 1886 年以来在该国出生的双胞胎的数据，并与住院患者登记处进行了交叉链接，后者提供了按照国际疾病分类（ICD）编码的出院诊断的全国覆盖范围。所有患有肾下 AAA 的双胞胎均被识别出来。计算了同卵（MZ）和异卵（DZ）双胞胎的一致性率和四分相关系数。四分相关系数是在假定潜在的 Liability 正态分布的情况下计算的，其中多个因素以累加的方式起作用，并且存在一个区分 AAA 和非 AAA 的阈值。MZ 双胞胎的一致性率和 Liability 相关系数高于 DZ 双胞胎，这表明遗传因素影响疾病的发展。使用结构方程模型技术（Mx 分析）来估计遗传效应以及共享和非共享环境因素对 AAA 发展的贡献。
结果
研究时登记的双胞胎有 172890 对，包括 265 对（81%为男性；平均年龄 72 岁；范围 48-94 岁）患有 AAA。有 7 对 MZ 和 5 对 DZ 同卵双胞胎以及 44 对 MZ 和 197 对 DZ 异卵双胞胎患有 AAA。MZ 和 DZ 对的先证者一致性率分别为 24%和 4.8%。MZ 对的四分相关系数为 0.71，DZ 对的四分相关系数为 0.31。MZ 双胞胎的比值比（OR）为 71（95%置信区间 [CI] 27-183），DZ 双胞胎的 OR 为 7.6（95% CI 3.0-19）。在结构方程模型中，遗传效应占表型变异的 70%（95% CI 0.33-0.83），共享环境效应占 0%（95% CI 0-0.27），非共享环境效应占 30%（95% CI 0.17-0.46）。
结论
这些数据提供了强有力的流行病学证据，表明遗传因素有助于动脉瘤的形成。MZ 双胞胎的一致性率和相关性高于 DZ 双胞胎，表明存在遗传效应。AAA 患者的 MZ 双胞胎有 24%的可能性患有该病。MZ 双胞胎患有 AAA 的 MZ 双胞胎的 AAA 风险是 MZ 双胞胎没有 AAA 的 MZ 双胞胎的 71 倍。估计遗传因素占总性状变异的 70%。其余的变异可以用非共享环境因素来解释，而共享环境因素没有作用。
Zotero 插件