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Observational Study
. 2021 Oct 14;13(19):23348-23360.
doi: 10.18632/aging.203629. Epub 2021 Oct 14.

Differential moderation effects of ApoE and 5-HTTLPR genotypes on social vulnerability in predicting mortality among community-dwelling middle-aged and older adults: a nationwide population-based study

Hsin-Yu Liu  1   2   3   4 , Li-Ning Peng  1   3 , Wei-Ju Lee  1   5 , Ming-Yueh Chou  1   6 , Chih-Kuang Liang  1   6 , Fei-Yuan Hsiao  7   8   9 , Ming-Hsien Lin  1   3 , Liang-Kung Chen  1   3   10
Affiliations
Observational Study

Differential moderation effects of ApoE and 5-HTTLPR genotypes on social vulnerability in predicting mortality among community-dwelling middle-aged and older adults: a nationwide population-based study

Hsin-Yu Liu et al. Aging (Albany NY). .

Abstract

Aging is a dynamic complex process involving social vulnerability over time. The social vulnerability index (SVI) was developed that predicted adverse health outcomes. This study examined effects between SVI status and two genotypes, apolipoprotein E (ApoE) and Serotonin transporter genotyping (5-HTTLPR), on all-cause mortality. Data from the Social Environment and Biomarkers of Aging Study (SEBAS) were obtained, and SVI was constructed using 32 self-reported items of social determinants. Data from 985 participants (age: 65.73 ± 9.47 years, 54.62% males) were obtained for analysis, and the median SVI was 0.35 (IQR 0.29-0.42) with a near normal distribution. Participants with a higher SVI were more likely to be women and have poor cognitive function, more depressive symptoms and poor physical function. Adjusted for age and sex, each incremental deficit in SVI was associated with a 12% increase in mortality risk (HR: 1.12, 95% CI: 1.04-1.20, p = 0.002). An interaction was found between ApoE and SVI but not 5-HTTLPR. The strata-specific hazard ratio confirmed that associations between SVI and mortality was only in non-ε4 carriers (HR: 1.15, 95% CI: 1.07-1.24, p < 0.001), and SVI did not significantly predict mortality among ε4 carriers (HR: 0.84, 95% CI: 0.65-1.10). Differential SVI effects on mortality among middle-age and older adults were identified. In conclusion, a higher SVI was associated with all-cause mortality among middle-aged and older adults, and the association was moderated by ApoE genotypes but not 5-HTTLPR. Further study is needed to evaluate the clinical efficacy of healthy aging intervention programs considering gene-environment interactions and social vulnerability.

Keywords: apolipoprotein E gene (ApoE); gene-environment interaction; serotonin transporter polymorphism (5-HTTLPR); social vulnerability; survival.

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Conflict of interest statement

CONFLICTS OF INTEREST: The authors declare no conflicts of interest related to this study.

Figures

Figure 1
Figure 1
The flow chart for inclusion of study participants.
Figure 2
Figure 2
Distribution of the social vulnerability index.
Figure 3
Figure 3
Survival analysis of participants with different social vulnerability index statuses.
Figure 4
Figure 4
Survival analysis of participants with different social vulnerability index and genotype statuses. (A) Social vulnerability index and 5-HTTLPR genotypes, and (B) social vulnerability index and ApoE genotypes.
See this image and copyright information in PMC

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