Oyen Nina, Poulsen Gry, Wohlfahrt Jan, Boyd Heather A, Jensen Peter K A, Melbye Mads
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
Circ Cardiovasc Genet. 2010 Apr;3(2):122-8. doi: 10.1161/CIRCGENETICS.109.890103. Epub 2010 Feb 20.
Variation within a single gene might produce different congenital heart defects (CHDs) within a family, which could explain the previously reported familial aggregation of discordant CHDs. We investigated whether certain groups of discordant CHDs are more common in families than others.
Using Danish national population and health registers, we identified CHDs among all singletons born in Denmark during 1977-2005 and their first-degree relatives. In a cohort of 1 711 641 persons, 16 777 had CHDs, which we classified into 14 phenotypes. We estimated relative risks of discordant CHDs by history of specific CHDs in first-degree relatives. The relative risk of any dissimilar CHD given the specified CHD in first-degree relatives was as follows: heterotaxia, 2.00 (95% CI, 0.96 to 4.17); conotruncal defects, 2.78 (95% CI, 2.12 to 3.66); atrioventricular septal defects, 2.25 (95% CI, 1.39 to 3.66); anomalous pulmonary venous return, 1.76 (95% CI, 0.66 to 4.64); left- and right-ventricular outflow tract obstruction, 2.55 (95% CI, 1.87 to 3.48) and 3.09 (95% CI, 2.03 to 4.71), respectively; isolated atrial septal defects, 2.76 (95% CI, 2.11 to 3.61); isolated ventricular septal defects, 2.27 (95% CI, 1.75 to 2.94); persistent ductus arteriosus, 1.92 (95% CI, 1.32 to 2.79); other specified CHDs, 3.29 (95% CI, 2.51 to 4.32); and unspecified CHDs, 2.30 (95% CI, 1.76 to 3.00). Relative risks for all pairwise combinations of discordant CHD phenotypes gave no indications that certain constellations of CHDs cluster more in families than others.
We documented strong familial aggregation of discordant CHD phenotypes. However, we observed no excess clustering of specific CHD phenotypes among the first-degree relatives.
单个基因内的变异可能在一个家族中产生不同的先天性心脏病（CHD），这可以解释先前报道的不一致性CHD的家族聚集现象。我们调查了某些不一致性CHD组在家族中是否比其他组更常见。
利用丹麦国家人口和健康登记册，我们确定了1977 - 2005年期间在丹麦出生的所有单胎婴儿及其一级亲属中的CHD。在一个1711641人的队列中，16777人患有CHD，我们将其分为14种表型。我们根据一级亲属中特定CHD的病史估计了不一致性CHD的相对风险。一级亲属中给定特定CHD时任何不同CHD的相对风险如下：内脏异位，2.00（95%CI，0.96至4.17）；圆锥动脉干畸形，2.78（95%CI，2.12至3.66）；房室间隔缺损，2.25（95%CI，1.39至3.66）；肺静脉异位引流，1.76（95%CI，0.66至4.64）；左心室和右心室流出道梗阻，分别为2.
