COL4A1 Is Associated With Arterial Stiffness by Genome-Wide Association Scan
Open accessAbstract
Background— Pulse wave velocity (PWV), a noninvasive index of central arterial stiffness, is a potent predictor of cardiovascular mortality and morbidity. Heritability and linkage studies have pointed toward a genetic component affecting PWV. We conducted a genome-wide association study to identify single-nucleotide polymorphisms (SNPs) associated with PWV. Methods and Results— The study cohort included participants from the SardiNIA study for whom PWV measures were available. Genotyping was performed in 4221 individuals, using either the Affymetrix 500K or the Affymetrix 10K mapping array sets (with imputation of the missing genotypes). Associations with PWV were evaluated using an additive genetic model that included age, age 2 , and sex as covariates. The findings were tested for replication in an independent internal Sardinian cohort of 1828 individuals, using a custom chip designed to include the top 43 nonredundant SNPs associated with PWV. Of the loci that were tested for association with PWV, the nonsynonymous SNP rs3742207 in the COL4A1 gene on chromosome 13 and SNP rs1495448 in the MAGI1 gene on chromosome 3 were successfully replicated ( P =7.08�10 −7 and P =1.06�10 −5 , respectively, for the combined analyses). The association between rs3742207 and PWV was also successfully replicated ( P =0.02) in an independent population, the Old-Order Amish, leading to an overall P =5.16�10 −8 . Conclusions— A genome-wide association study identified a SNP in the COL4A1 gene that was significantly associated with PWV in 2 populations. Collagen type 4 is the major structural component of basement membranes, suggesting that previously unrecognized cell-matrix interactions may exert an important role in regulating arterial stiffness.
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A single nucleotide polymorphism in the COL4A1 gene was associated with pulse wave velocity, an index of arterial stiffness, in a population.
“a single nucleotide polymorphism in the COL4A1 gene was associated with pulse wave velocity, an index of arterial stiffness, in a population.180”
A variant in COL4A1 was associated with increased arterial stiffness.
“A variant in COL4A1 was associated with increased arterial stiffness 44 .”
From Connecting proteomics and genomics to identify causal biomarkers specific for aortic valve stenosis (2025) · cites this paper as [44]
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“A variant in COL4A1 was associated with increased arterial stiffness 44 .”
- Authors
- Tarasov, K. V., Sanna, S., Scuteri, A., Strait, J. B., Orrù, M., Parsa, A., Lin, P.-I., Maschio, A., Lai, S., Piras, M. G., Masala, M., Tanaka, T., Post, W., O'Connell, J. R., Schlessinger, D., Cao, A., Nagaraja, R., Mitchell, B. D., Abecasis, G. R., Shuldiner, A. R., Uda, M., Lakatta, E. G., & Najjar, S. S.
- Affiliations
- University of Maryland, Baltimore (US)
- From the Laboratory of Cardiovascular Science (K.V.T., J.B.S., E.G.L., S.S.N.), Laboratory of Genetics (K.V.T., J.B.S., D.S., R.N.), Clinial Research Branch (T.T.), Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Md; Istituto di Neurogenetica e Neurofarmacologia (INN) (S.S., M.O., A.M., S.L., G.P., M.M., A.C., M.U.), Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monseratto, Monserrato, Cagliari, Italy; Unitá Operativa...
- ORCID
- Venue
- Circulation: Cardiovascular Genetics
- Published
- 2009-04
- Volume
- 2
- Issue
- 2
- Pages
- 151-158
- ISSN
- 1942-325X (ISSN-L)
- 1942-3268
- PMC
- PMC2801872
- OpenAlex
- W2065566863
- Cited by
- 104
- References
- 46
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 3 · 2022: 3 · 2021: 2 · 2020: 3 · 2019: 7 · 2018: 8 · 2017: 8 · 2016: 2 · 2015: 23 · 2014: 10 · 2013: 8 · 2012: 6
- FWCI
- 3.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Circulation Cardiovascular Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- UNICA IRIS Institutional Research Information System (University of Cagliari) (submittedVersion)
- UnissResearch (Università degli Studi di Sassari) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (N01-AG-12109, Z01AG000672, Z01AG000856)
- National Heart, Lung, and Blood Institute (U01HL72515, T32HL072751, U01HL072515)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK072488)
- National Center for Research Resources (M01RR016500, M01RR 16500)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
- Keywords
- COL4A1, arterial stiffness, pulse wave velocity, single nucleotide polymorphisms, MAGI1, type IV collagen, basement membrane, genetic association, cardiovascular risk, Sardinia, Old Order Amish
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Arteries, Cardiovascular Diseases, Chromosomes, Human, Pair 13, Female, Humans, Male, Middle Aged, Cohort Studies, Polymorphism, Single Nucleotide, Collagen Type IV, Genome-Wide Association Study, Young Adult
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