Unique lipoprotein phenotype and genotype associated with exceptional longevity
Unique lipoprotein phenotype and genotype associated with exceptional longevity
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DOI：
10.1001/jama.290.15.2030
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发表时间：
2003-10-15
影响因子：
120.7
通讯作者：
Shuldiner, AR
中科院分区：
文献类型：
--
作者：
Barzilai, N;Atzmon, G;Shuldiner, AR
超常长寿的个体在年龄相关疾病的发病方面具有较低的发病率和/或显著的延迟，其家庭成员可能遗传调节衰老过程和疾病易感性的生物学因素。目的确定与人类长寿表型相关或可靠定义人类长寿表型的特定生物学和遗传因素。设计、环境和参与者在病例对照设计中，从1998年至2002年招募了213名异常长寿的德系犹太人先证者（平均[SDI年龄，98.2[5.3]岁）及其后代（n=216；平均[SD]年龄，68.3[6.7]岁），同时接受了年龄匹配的德系犹太人对照组（n=258）和Framingham后代研究的参与者（n= 589）作为对照组。主要观察指标：采用详细的问卷调查、体格检查和血液样本，包括通过质子核磁共振评估脂质和脂蛋白亚类水平和颗粒大小。对参与脂蛋白及其颗粒大小调控的胆固醇酯转移蛋白（CETP）基因密码子405异亮氨酸-缬氨酸（1405V）变异进行基因分型。结果先证者的高密度脂蛋白（HDL）和低密度脂蛋白（LDL）颗粒大小明显高于对照组（P= 0.001），与血浆中HDL和LDL胆固醇以及载脂蛋白A1和b的水平无关。这种表型在先证者的后代中也是典型的，但在年龄匹配的对照组中却没有。在没有高血压或心血管疾病的后代和对照组中，HDL和LDL颗粒大小明显较大（P= 0.001和P= 0.008）。此外，在没有代谢综合征的后代和对照组中，脂蛋白颗粒大小而不是血浆LDL水平显著升高(P
Context Individuals with exceptional longevity have a lower incidence and/or significant delay in the onset of age-related disease, and their family members may inherit biological factors that modulate aging processes and disease susceptibility.Objective To identify specific biological and genetic factors that are associated with or reliably define a human longevity phenotype.Design, Setting, and Participants In a case-control design, 213 Ashkenazi Jewish probands with exceptional longevity (mean [SDI age, 98.2 [5.3] years) and their offspring (n=216; mean [SD] age, 68.3 [6.7] years) were recruited from 1998 to 2002, while an age-matched control group of Ashkenazi Jews (n=258) and participants from the Framingham Offspring Study (n = 589) were accepted as control groups.Main Outcome Measures Detailed questionnaires, physical examination, and blood samples were taken, including assessment of lipids and lipoprotein subclass levels and particle sizes by proton nuclear magnetic resonance. Samples were also genotyped for the codon 405 isoleucine to valine (1405V) variation in the cholesteryl ester transfer protein (CETP) gene, which is involved in regulation of lipoprotein and its particle sizes.Results High-density lipoprotein (HDL) and low-density lipoprotein (LDL) particle sizes were significantly higher in probands compared with both control groups (P=.001 for both), independent of plasma levels of HDL and LDL cholesterol and apolipoprotein A1 and B. This phenotype was also typical of the proband's offspring but not of the age-matched controls. The HDL and LDL particle sizes were significantly larger in offspring and controls without hypertension or cardiovascular disease, (P=.001 and P=.008, respectively). Furthermore, lipoprotein particle sizes, but not plasma LDL levels, were significantly higher in offspring and controls without the metabolic syndrome (P