The role of lipid-related genes, aging-related processes, and environment in healthspan.
The role of lipid-related genes, aging-related processes, and environment in healthspan.
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DOI：
10.1111/acel.12046
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发表时间：
2013-04
期刊：
影响因子：
7.8
通讯作者：
Yashin AI
中科院分区：
文献类型：
--
作者：
Kulminski AM;Culminskaya I;Arbeev KG;Ukraintseva SV;Stallard E;Arbeeva L;Yashin AI
衰老相关特征固有的复杂性可能会阻碍阐明健康寿命遗传起源的进展。我们重点关注弗雷明汉心脏研究中的两代人，即原始 (FHS) 和后代 (FHSO) 队列，以确定不断变化的环境中的衰老相关过程是否会对候选基因（载脂蛋白 E (APOE) e2/3/4 多态性）和全基因组（APOB rs1042034 (C/T)）研究中发现的脂质相关基因在调节总胆固醇 (TC) 和心血管疾病发作中的作用产生重大影响（化学气相沉积）。我们证明，APOE e4 等位基因和 APOB CC 基因型在不同年龄和不同环境下的 CVD 病因中可以发挥有害、中性和保护性的性别特异性作用。我们记录了 e4 等位基因在 CVD 发病中的拮抗作用，其特点是对 FHS 参与者在年轻时产生有害影响 (RR≤75yrs=1.49，p=7.5×10−4)，在老年时产生保护作用 (RR76+yrs=0.77，p=0.044)。我们发现，错误地忽视衰老的作用会抵消 e4 等位基因在此样本中的显着影响（RR=0.92，p=0.387）。介导 CVD 遗传效应的主要生物遗传途径可能与 APOB 的脂质代谢比 APOE 更相关。衰老相关过程可以调节不同年龄的同一个体与 TC 的遗传关联强度。我们发现相同 APOE 和 APOB 等位基因对不同世代的 CVD 和 TC 的影响存在显着差异。结果表明，不断变化的环境中与衰老相关的过程可能在健康寿命的遗传学中发挥关键作用。详细的系统综合分析可能会大大推进进展。
The inherent complexity of aging-related traits can temper progress in unraveling the genetic origins of healthspan. We focus on two generations in the Framingham Heart Study, the original (FHS) and offspring (FHSO) cohorts, to determine whether aging-related processes in changing environments can substantially impact the role of lipid-related genes discovered in candidate-gene (the apolipoprotein E (APOE) e2/3/4 polymorphism) and genome-wide (the APOB rs1042034 (C/T)) studies, in regulation of total cholesterol (TC) and onset of cardiovascular disease (CVD). We demonstrate that the APOE e4 allele and APOB CC genotype can play detrimental, neutral, and protective sex-specific roles in the etiology of CVD at different ages and in different environments. We document antagonistic roles for the e4 allele in the onset of CVD characterized by detrimental effects at younger ages (RR≤75yrs=1.49, p=7.5×10−4) and protective effects at older ages (RR76+yrs=0.77, p=0.044) for FHS participants. We found that disregarding the role of aging erroneously nullifies the significant effects of the e4 allele in this sample (RR=0.92, p=0.387). The leading bio-genetic pathways mediating genetic effects on CVD may be more relevant to lipid metabolism for APOB than APOE. Aging-related processes can modulate the strength of genetic associations with TC in the same individuals at different chronological ages. We found substantial differences in the effects of the same APOE and APOB alleles on CVD and TC across generations. The results suggest that aging-related processes in changing environments may play key roles in the genetics of healthspan. Detailed systemic integrative analyses may substantially advance the progress.
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影响因子：
8.7
作者：
KUUSISTO, J;MYKKANEN, L;LAAKSO, M
通讯作者：
LAAKSO, M
DOI：
10.1196/annals.1396.050
发表时间：
2007-01-01
期刊：
HEALTHY AGING AND LONGEVITY
影响因子：
--
作者：
Olshansky, S. Jay;Perry, Daniel;Butler, Robert N.
通讯作者：
Butler, Robert N.
影响因子：
7.8
作者：
Kulminski AM;Culminskaya I;Ukraintseva SV;Arbeev KG;Arbeeva L;Wu D;Akushevich I;Land KC;Yashin AI
通讯作者：
Yashin AI
影响因子：
2.1
作者：
JARVIK, GP;AUSTIN, MA;DEEB, S
通讯作者：
DEEB, S
影响因子：
37.8
作者：
Ilveskoski, E;Perola, M;Karhunen, PJ
通讯作者：
Karhunen, PJ