Key result
The minor G allele of SNP rs5068 was associated with a decreased incidence of sustained orthostatic hypotension at 40 seconds compared to the A allele (IRR 0.45; 95% CI 0.29-0.72; p=0.001).
Why the study?
Orthostatic hypotension increases the risk of trauma and cardiovascular events, and newly identified genetic variants influence orthostatic blood pressure, prompting investigation into whether candidate gene loci associate with orthostatic blood pressure responses in older adults.
Do specific blood pressure-associated gene variants influence the risk of orthostatic hypotension in adults aged ≥50 years?
Observational (n=3,430)
Do specific blood pressure-associated gene variants influence the risk of orthostatic hypotension in adults aged ≥50 years?
Relative Risk: 0.45 (95% CI 0.29–0.72)
p-value: p=0.001
Genetic variants linked to blood pressure responses appear to have only a weak impact on orthostatic hypotension in older adults, with one specific SNP (rs5068) showing a significant protective association.
May support genetic risk stratification for orthostatic hypotension; hypothesis-generating and should not yet change practice.
Orthostatic hypotension (OH) is associated with increased risk of trauma and cardiovascular events. Recent studies have identified new genetic variants that influence orthostatic blood pressure (BP). The aim of this study was to investigate the associations of candidate gene loci with orthostatic BP responses in older adults. A total of 3,430 participants aged ≥50 years from The Irish Longitudinal Study on Ageing (TILDA) with BP measures and genetic data from 12 single-nucleotide polymorphism (SNP) linked to BP responses were analyzed. Orthostatic BP responses were recorded at each 10 s interval and were defined as OH (SBP drop ≥20 mmHg or DBP drop ≥10 mmHg) at the time-points 40, 90, and 110 s. We defined sustained OH (SOH) as a drop that exceeded consensus BP thresholds for OH at 40, 90, and 110 s after standing. Logistic regression analyses modeled associations between the candidate SNP alleles and OH. We report no significant associations between OH and measured SNPs after correction for multiple comparisons apart from the SNP rs5068 where proportion of the minor allele was significantly different between cases and controls for SOH 40 (p = .002). After adjustment for covariates in a logistic regression, those with the minor G allele (compared to the A allele) had a decreased incidence rate ratio (IRR) for SOH 40 (IRR 0.45, p = .001, 95% CI 0.29-0.72). Only one SNP linked with increased natriuretic peptide concentrations was associated with OH. These results suggest that genetic variants may have a weak impact on OH but needs verification in other population studies.
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Laird et al. (2019) conducted an observational in Orthostatic hypotension (n=3,430). SNP rs5068 minor G allele vs. A allele was evaluated on Sustained orthostatic hypotension at 40 seconds (SOH 40) (IRR 0.45, 95% CI 0.29-0.72, p=0.001). The minor G allele of SNP rs5068 was associated with a decreased incidence of sustained orthostatic hypotension at 40 seconds compared to the A allele (IRR 0.45; 95% CI 0.29-0.72; p=0.001).
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