In:
Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 8 ( 2022-1-14)
Abstract:
Serum calciprotein particle maturation time (T 50 ), a measure of vascular calcification propensity, is associated with cardiovascular morbidity and mortality. We aimed to identify genetic loci associated with serum T 50 and study their association with cardiovascular disease and mortality. Methods: We performed a genome-wide association study of serum T 50 in 2,739 individuals of European descent participating in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) study, followed by a two-sample Mendelian randomization (MR) study to examine causal effects of T 50 on cardiovascular outcomes. Finally, we examined associations between T 50 loci and cardiovascular outcomes in 8,566 community-dwelling participants in the Rotterdam study. Results: We identified three independent genome-wide significant single nucleotide polymorphism (SNPs) in the AHSG gene encoding fetuin-A: rs4917 ( p = 1.72 × 10 −101 ), rs2077119 ( p = 3.34 × 10 −18 ), and rs9870756 ( p = 3.10 × 10 −8 ), together explaining 18.3% of variation in serum T 50 . MR did not demonstrate a causal effect of T 50 on cardiovascular outcomes in the general population. Patient-level analyses revealed that the minor allele of rs9870756, which explained 9.1% of variation in T 50 , was associated with a primary composite endpoint of all-cause mortality or cardiovascular disease [odds ratio (95% CI) 1.14 (1.01–1.28)] and all-cause mortality alone [1.14 (1.00–1.31)] . The other variants were not associated with clinical outcomes. In patients with type 2 diabetes or chronic kidney disease, the association between rs9870756 and the primary composite endpoint was stronger [OR 1.40 (1.06–1.84), relative excess risk due to interaction 0.54 (0.01–1.08)]. Conclusions: We identified three SNPs in the AHSG gene that explained 18.3% of variability in serum T 50 levels. Only one SNP was associated with cardiovascular outcomes, particularly in individuals with type 2 diabetes or chronic kidney disease.
Type of Medium:
Online Resource
ISSN:
2297-055X
DOI:
10.3389/fcvm.2021.809717
DOI:
10.3389/fcvm.2021.809717.s001
DOI:
10.3389/fcvm.2021.809717.s002
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2022
detail.hit.zdb_id:
2781496-8
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