Center for the Study of Aging and Human Development, Geriatrics Division of School of Medicine, Duke University, Box 3003 Durham, NC 27710, USA.
BMC Geriatr. 2013 Sep 9;13:91. doi: 10.1186/1471-2318-13-91.
Existing literature indicates that ADRB2 gene is associated with health and longevity, but none of previous studies investigated associations of carrying the ADRB2 minor alleles and interactions between ADRB2 genotypes and social/behavioral factors(GxE) with health outcomes at advanced ages. This study intends to fill in this research gap.
We conducted an exploratory analysis, using longitudinal survey phenotype/genotype data from 877 oldest-old aged 90+. To estimate association of GxE interactions with health outcome, adjusted for the potential correlation between genotypes and social/behavioral factors and various other potentially confounding factors, we develop and test an innovative three-step procedure which combines logistic regression and structural equation methods.
Interaction between regular exercise and carrying rs1042718 minor allele is significantly and positively associated with good cognitive function; interaction between regular exercise and carrying rs1042718 or rs1042719 minor allele is significantly and positively associated with self-reported good health; and interaction between social-leisure activities and carrying rs1042719 minor allele is significantly and positively associated with self-reported good health. Carrying rs1042718 or rs1042719 minor alleles is significantly and negatively associated with negative emotion, but the ADRB2 SNPs are not significantly associated with cognitive function and self-reported health. Our structural equation analysis found that, adjusted for the confounding effects of correlation of the ADRB2 SNPs with negative emotion, interaction between negative emotion and carrying rs1042718 or rs1042719 minor allele is significantly and negatively associated with cognitive function. The positive association of regular exercise and social-leisure activities with cognitive function and self-reported health, and negative association of negative emotion with cognitive function, were much stronger among carriers of rs1042718 or rs1042719 alleles, compared to the non-carriers.
The results indicate significant positive associations of interactions between social/behavioral factors and the ADRB2 genotypes with health outcomes of cognitive function and self-reported health, and negative associations of carrying rs1042718 or rs1042719 minor alleles with negative emotion, at advanced ages in China. Our findings are exploratory rather than causal conclusions. This study implies that near-future health promotion programs considering individuals' genetic profiles, with appropriate protection of privacy/confidentiality, would yield increased benefits and reduced costs to the programs and their participants.
现有文献表明 ADRB2 基因与健康和长寿有关，但之前的研究都没有调查携带 ADRB2 次要等位基因与 ADRB2 基因型和社会/行为因素（GxE）之间的相互作用与高龄时的健康结果之间的关系。本研究旨在填补这一研究空白。
我们进行了一项探索性分析，使用来自 877 名 90 岁以上的最年长参与者的纵向调查表型/基因型数据。为了估计 GxE 相互作用与健康结果的关联，我们调整了基因型与社会/行为因素之间的潜在相关性以及各种其他潜在混杂因素，我们开发并测试了一种创新的三步骤程序，该程序结合了逻辑回归和结构方程方法。
有规律的锻炼与携带 rs1042718 次要等位基因之间的相互作用与认知功能良好显著正相关；有规律的锻炼与携带 rs1042718 或 rs1042719 次要等位基因之间的相互作用与自我报告的健康状况良好显著正相关；社会休闲活动与携带 rs1042719 次要等位基因之间的相互作用与自我报告的健康状况良好显著正相关。携带 rs1042718 或 rs1042719 次要等位基因与负面情绪显著负相关，但 ADRB2 SNPs 与认知功能和自我报告的健康状况无显著相关性。我们的结构方程分析发现，在调整 ADRB2 SNPs 与负面情绪的相关性的混杂效应后，负面情绪与携带 rs1042718 或 rs1042719 次要等位基因之间的相互作用与认知功能显著负相关。与非携带者相比，有规律的锻炼和社会休闲活动与认知功能和自我报告的健康状况呈正相关，而负面情绪与认知功能呈负相关，这种相关性在携带 rs1042718 或 rs1042719 等位基因的人群中更为明显。
这些结果表明，在中国高龄人群中，社会/行为因素与 ADRB2 基因型之间的相互作用与认知功能和自我报告的健康结果呈显著正相关，携带 rs1042718 或 rs1042719 次要等位基因与负面情绪呈负相关。我们的研究结果是探索性的，而不是因果关系的结论。这一研究表明，在考虑个体遗传特征的情况下，制定和实施适当保护隐私/机密性的未来健康促进计划，将为计划及其参与者带来更大的收益和更低的成本。
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