Delling Francesca N, Li Xinjun, Li Shuo, Yang Qiong, Xanthakis Vanessa, Martinsson Andreas, Andell Pontus, Lehman Birgitta T, Osypiuk Ewa W, Stantchev Plamen, Zöller Bengt, Benjamin Emelia J, Sundquist Kristina, Vasan Ramachandran S, Smith J Gustav
From the Boston University's and National Heart, Lung and Blood Institute's Framingham Heart Study, MA (F.N.D., B.T.L., E.W.O., P.S., E.J.B., R.S.V.); Cardiovascular Division, Department of Medicine, University of California San Francisco (F.N.D.); Center for Primary Health Care Research, Lund University, Malmö, Sweden (X.L., B.Z., K.S.); Department of Biostatistics (S.L., Q.Y., V.X.), Department of Epidemiology (V.X., E.J.B., R.S.V.), and Cardiology and Preventive Medicine Sections, Department of Medicine (E.J.B., R.S.V.), Boston University School of Medicine, MA; Department of Cardiology, Clinical Sciences, Lund University, Sweden (A.M., P.A., J.G.S.); and Skåne University Hospital, Lund, Sweden (A.M., P.A., J.G.S.).
Circ Cardiovasc Genet. 2017 Oct;10(5). doi: 10.1161/CIRCGENETICS.117.001736.
Familial aggregation has been described for primary mitral regurgitation (MR) caused by mitral valve prolapse. We hypothesized that heritability of MR exists across different MR subtypes including nonprimary MR.
Study participants were FHS (Framingham Heart Study) Generation 3 (Gen 3) and Gen 2 cohort participants and all adult Swedish siblings born after 1932 identified in 1997 and followed through 2010. MR was defined as ≥ mild regurgitation on color Doppler in FHS and from codes in Sweden. We estimated the association of sibling MR with MR in Gen 2/Gen 3/Swedish siblings. We also estimated heritability of MR in 539 FHS pedigrees (7580 individuals). Among 5132 FHS Gen 2/Gen 3 participants with sibling information, 1062 had MR. Of siblings with sibling MR, 28% (500/1797) had MR compared with 17% (562/3335) without sibling MR (multivariable-adjusted odds ratio, 1.20; 95% confidence interval [CI], 1.01-1.43; =0.04). When we combined parental and sibling data in FHS pedigrees, heritability of MR was estimated at 0.15 (95% CI, 0.07-0.23), 0.12 (95% CI, 0.04-0.20) excluding mitral valve prolapse, and 0.44 (95% CI, 0.15-0.73) for ≥ moderate MR only (all <0.05). In Sweden, sibling MR was associated with a hazard ratio of 3.57 (95% CI, 2.21-5.76; <0.001) for development of MR.
Familial clustering of MR exists in the community, supporting a genetic susceptibility common to primary and nonprimary MR. Further studies are needed to elucidate the common regulatory pathways that may lead to MR irrespective of its cause.
二尖瓣脱垂所致原发性二尖瓣反流（MR）存在家族聚集现象。我们推测，MR的遗传力在包括非原发性MR在内的不同MR亚型中均存在。
研究参与者为弗雷明汉心脏研究（FHS）第3代（Gen 3）和第2代队列参与者，以及1997年确定的1932年后出生的所有成年瑞典同胞，并随访至2010年。在FHS中，MR定义为彩色多普勒显示反流≥轻度，在瑞典则根据编码确定。我们估计了同胞MR与第2代/第3代/瑞典同胞中MR的关联。我们还估计了539个FHS家系（7580人）中MR的遗传力。在5132名有同胞信息的FHS第2代/第3代参与者中，1062人患有MR。在有同胞患MR的同胞中，28%（500/1797）患有MR，而无同胞患MR的同胞中这一比例为17%（562/3335）（多变量调整优势比为1.20；95%置信区间[CI]为1.01 - 1.43；P = 0.04）。当我们将FHS家系中的父母和同胞数据合并时，MR的遗传力估计值为0.15（95% CI为0.07 - 0.23），排除二尖瓣脱垂时为0.12（95% CI为0.04 - 0.20），仅对于≥中度MR为0.44（95% CI为0.15 - （此处原文缺失完整数据）0.73）（均P < 0.05）。在瑞典，同胞患MR与发生MR的风险比为3.57（95% CI为2.21 - 5.76；P < 0.001）。结论：社区中存在MR的家族聚集现象，支持原发性和非原发性MR存在共同的遗传易感性。需要进一步研究以阐明可能导致MR的共同调控途径，而不论其病因如何。 （注：原文中最后一个95% CI数据缺失完整内容，已按实际翻译情况说明）
