Τίτλος:
Association between 9p21-23 Locus and Frailty in a Community-Dwelling
Greek Population: Results from the Hellenic Longitudinal Investigation
of Ageing and Diet
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Background Frailty is a complex geriatric syndrome arising from a
combination of genetic and environmental factors and is associated with
adverse health outcomes and mortality. A recent study reported an
association between variants of the 9p21-23 locus, associated with a
number of age-related disorders, including Alzheimer’s disease (AD), and
frailty. Frailty has been associated with increased risk of developing
AD and it has been proposed that frailty burden may modify AD clinical
presentation. In view of the overlapping genetic architecture between
the two disorders, it is noteworthy to conduct studies to uncover risk
variants that contribute to both AD and frailty. The purpose of this
study is to test the reproducibility of the association of 9p21-23 locus
with frailty in a population that is ethnically different from previous
work and in the context of multidimensional definitions of frailty that
will allow us to examine the potential impact to domains pertaining to
AD pathology. Methods We operationalized frailty according two
definitions and the corresponding instruments, the Frailty Index (FI)
and the Tilburg Frailty Indicator (TFI) and we determined genotypes of
eight alleles previously identified as risk increasing for frailty in
1172 community-dwelling older participants (57% females) from the
HELIAD study with a mean age of 74 years old. We cross-sectionally
investigated the association between risk alleles and frailty, as well
as with specific components of each definition using linear regression
analyses adjusted for age, sex and years of education. Results Compared
to non-carriers, carriers of rs7038172 C risk allele, were associated
with a higher FI Score (beta=0.089, p=0.002). Similarly, we found a
positive association between the presence of at least one rs7038172 C
variant and TFI score (beta=0.053, p=0.04). Moreover, the rs7038172
variant was associated, irrespectively of dementia status, with the
memory and psychological domain of FI and TFI, respectively. Conclusion
Our study confirms the association of the rs7038172 C allele with the
frailty syndrome in a Greek population and in the context of
multidimensional definitions of frailty. Furthermore, we report novel
associations between this allele and the memory domain of FI and the
psychological domain of TFI, that includes memory problems on its
components. Given that frailty burden has been shown to modify the AD
clinical presentation, it is likely that rs7038172 C allele may
accelerate the transition of AD or frailty to dementia Overall, our
study corroborates the role of the 9p21-23 region in frailty development
and draw potential links with AD pathology.
Συγγραφείς:
Mourtzi, N.
Hatzimanolis, A.
Xiromerisiou, G.
Ntanasi, E.
and Georgakis, M. K.
Ramirez, A.
Heilmann-Heimbach, S. and
Grenier-Boley, B.
Lambert, J. C.
Yannakoulia, M.
Kosmidis,
M.
Dardiotis, E.
Hadjigeorgiou, G.
Sakka, P.
Scarmeas,
Nikolaos
Περιοδικό:
JPAD: The Journal of Prevention of Alzheimers Disease
Εκδότης:
SPRINGER BASEL AG
Λέξεις-κλειδιά:
Frailty; 9p21-23 locus; Alzheimer; genetics
DOI:
10.14283/jpad.2022.2
