Ovid Technologies (Wolters Kluwer Health)
Hypertension
,  volume 81 ,  issue 10 ,  pages 2101-2112

Genetic Variance in Heparan Sulfation Is Associated With Salt Sensitivity

Jetta J. Oppelaar 1, 2
, 
Bart Ferwerda 3
, 
Mohamed A. Romman 1
, 
Ghazalah N. Sahebdin 1
, 
Aeilko H. Zwinderman 3
, 
Henrike Galenkamp 4
, 
S. M. Boekholdt 2, 5
, 
Bert-Jan H. van den Born 2, 4, 6
, 
Rik Olde Engberink 1, 2
, 
Liffert Vogt 1, 2
1
 
Department of Internal Medicine, Section of Nephrology (J.J.O., M.A.R., G.N.S., R.H.G.O.E., L.V.)
2
 
Amsterdam Cardiovascular Sciences, the Netherlands (J.J.O., R.H.G.O.E., L.V., S.M.B., B.-J.H.B.). | 
3
 
Department of Clinical Epidemiology and Biostatistics (B.F., A.H.Z.)
4
 
Department of Public and Occupational Health, Amsterdam Public Health (H.G., B.-J.H.B.)
5
 
Department of Cardiology (S.M.B.)
6
 
Publication type: Journal Article
Publication date: 2024-10-01
Ovid Technologies (Wolters Kluwer Health)
scimago Q1
wos Q1
SJR: 2.788
CiteScore: 13.1
Impact factor: 8.2
ISSN: 0194911X, 15244563, 23071095, 22241485
Abstract
BACKGROUND:

High heritability of salt sensitivity suggests an essential role for genetics in the relationship between sodium intake and blood pressure (BP). The role of glycosaminoglycan genes, which are crucial for salinity tolerance, remains to be elucidated.

METHODS:

Interactions between 54 126 variants in 130 glycosaminoglycan genes and daily sodium excretion on BP were explored in 20 420 EPIC-Norfolk (European Prospective Investigation Into Cancer in Norfolk) subjects. The UK Biobank (n=414 132) and the multiethnic HELIUS study (Healthy Life in an Urban Setting; n=2239) were used for validation. Afterward, the urinary glycosaminoglycan composition was studied in HELIUS participants (n=57) stratified by genotype and upon dietary sodium loading in a time-controlled crossover intervention study (n=12).

RESULTS:

rs2892799 in NDST3 (heparan sulfate N-deacetylase/N-sulfotransferase 3) showed the strongest interaction with sodium on mean arterial pressure (false discovery rate 0.03), with higher mean arterial pressure for the C allele in high sodium conditions. Also, rs9654628 in HS3ST5 (heparan sulfate-glucosamine 3-sulfotransferase 5) showed an interaction with sodium on systolic BP (false discovery rate 0.03). These interactions were multiethnically validated. Stratifying for the rs2892799 genotype showed higher urinary expression of N-sulfated heparan sulfate epitope D0S0 for the T allele. Conversely, upon dietary sodium loading, urinary D0S0 expression was higher in participants with stable BP after sodium loading, and sodium-induced effects on this epitope were opposite in individuals with and without BP response to sodium.

CONCLUSIONS:

The C allele of rs2892799 in NDST3 exhibits higher BP in high sodium conditions when compared with low sodium conditions, whereas no differences were detected for the T allele. Concomitantly, both alleles demonstrate distinct expressions of D0S0, which, in turn, correlates with sodium-mediated BP elevation. These findings underscore the potential significance of genetic glycosaminoglycan variation in human BP regulation.

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GOST Copy
Oppelaar J. J. et al. Genetic Variance in Heparan Sulfation Is Associated With Salt Sensitivity // Hypertension. 2024. Vol. 81. No. 10. pp. 2101-2112.
GOST all authors (up to 50) Copy
Oppelaar J. J., Ferwerda B., Romman M. A., Sahebdin G. N., Zwinderman A. H., Galenkamp H., Boekholdt S. M., van den Born B. H., Engberink R. O., Vogt L. Genetic Variance in Heparan Sulfation Is Associated With Salt Sensitivity // Hypertension. 2024. Vol. 81. No. 10. pp. 2101-2112.
RIS |
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RIS Copy
TY - JOUR
DO - 10.1161/hypertensionaha.124.23421
UR - https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.124.23421
TI - Genetic Variance in Heparan Sulfation Is Associated With Salt Sensitivity
T2 - Hypertension
AU - Oppelaar, Jetta J.
AU - Ferwerda, Bart
AU - Romman, Mohamed A.
AU - Sahebdin, Ghazalah N.
AU - Zwinderman, Aeilko H.
AU - Galenkamp, Henrike
AU - Boekholdt, S. M.
AU - van den Born, Bert-Jan H.
AU - Engberink, Rik Olde
AU - Vogt, Liffert
PY - 2024
DA - 2024/10/01
PB - Ovid Technologies (Wolters Kluwer Health)
SP - 2101-2112
IS - 10
VL - 81
PMID - 39247955
SN - 0194-911X
SN - 1524-4563
SN - 2307-1095
SN - 2224-1485
ER -
BibTex |
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BibTex (up to 50 authors) Copy
@article{2024_Oppelaar,
author = {Jetta J. Oppelaar and Bart Ferwerda and Mohamed A. Romman and Ghazalah N. Sahebdin and Aeilko H. Zwinderman and Henrike Galenkamp and S. M. Boekholdt and Bert-Jan H. van den Born and Rik Olde Engberink and Liffert Vogt},
title = {Genetic Variance in Heparan Sulfation Is Associated With Salt Sensitivity},
journal = {Hypertension},
year = {2024},
volume = {81},
publisher = {Ovid Technologies (Wolters Kluwer Health)},
month = {oct},
url = {https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.124.23421},
number = {10},
pages = {2101--2112},
doi = {10.1161/hypertensionaha.124.23421}
}
MLA
Cite this
MLA Copy
Oppelaar, Jetta J., et al. “Genetic Variance in Heparan Sulfation Is Associated With Salt Sensitivity.” Hypertension, vol. 81, no. 10, Oct. 2024, pp. 2101-2112. https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.124.23421.