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Increased cardiovascular mortality in females with the a/a genotype of the SNPs rs1478604 and rs2228262 of thrombospondin-1
Linköping Univ, Inst Med & Hlth Sci, Div Cardiovasc Med, Dept Med & Hlth Sci, Fac Hlth Sci, SE-58185 Linköping, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Jönköping Cty, Div Med Diagnost, Dept Lab Med, Jönköping, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.ORCID iD: 0000-0002-3655-2419
2020 (English)In: BMC Medical Genetics, E-ISSN 1471-2350, Vol. 21, no 1, article id 179Article in journal (Refereed) Published
Abstract [en]

Background

Cardiovascular diseases are still the major cause of death in the Western world, with different outcomes between the two genders. Efforts to identify those at risk are therefore given priority in the handling of health resources. Thrombospondins (TSP) are extracellular matrix proteins associated with cardiovascular diseases. The aim of this study was to investigate variations in single nucleotide polymorphisms (SNPs) of TSP-1 and plasma expression, and associations with mortality from a gender perspective.

Methods

A population of 470 community-living persons were invited to participate. The participants were followed for 7.9 years and underwent a clinical examination and blood sampling. SNP analyses of TSP-1 rs1478604 and rs2228262 using allelic discrimination and plasma measurement of TSP-1 using ELISA were performed,

Results

During the follow-up period, 135 (28.7%) all-cause and 83 (17.7%) cardiovascular deaths were registered.

In the female population, the A/A genotype of rs2228262 and the T/T genotype of rs1478604 exhibited significantly more cardiovascular deaths compared with the A/G and G/G, or the T/C and C/C genotypes amalgamated (rs2228262: 13.7% vs 2.0%; Χ2:5.29; P = 0.02; rs1478604:17.7% vs 4.7%; Χ2:9.50; P = 0.002). Applied in a risk evaluation, the A/A, or T/T genotypes exhibited an increased risk of cardiovascular mortality (rs2228262: HR: 7.1; 95%CI 1.11–45.8; P = 0.04; rs1478604: HR: 3.18; 95%CI 1.35–7.50; p = 0.008). No differences among the three genotypes could be seen in the male group.

Conclusion

In this study the female group having the A/A genotype of rs2228262, or the T/T genotype of rs1478604 of TSP-1 exhibited higher cardiovascular mortality after a follow-up of almost 8 years. No corresponding genotype differences could be found in the male group. Genotype evaluations should be considered as one of the options to identify individuals at risk. However, this study should be regarded as hypothesis-generating, and more research in the field is needed.

Place, publisher, year, edition, pages
2020. Vol. 21, no 1, article id 179
Keywords [en]
TSP-1, Genotypes, Elderly, Genders, Mortality
National Category
Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:uu:diva-423170DOI: 10.1186/s12881-020-01118-7ISI: 000571707600001PubMedID: 32917134OAI: oai:DiVA.org:uu-423170DiVA, id: diva2:1501850
Funder
Swedish Heart Lung FoundationRegion ÖstergötlandAvailable from: 2020-11-18 Created: 2020-11-18 Last updated: 2024-01-17Bibliographically approved

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Shamoun, LevarWågsäter, Dick

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