Gene polymorphisms of fibronectin rs2289202 and fibrillin 2 rs331069 associate with vascular disease, the TAMRISK study
- Authors:
- Tarja Kunnas
- Tiina Solakivi
- Seppo T. Nikkari
View Affiliations
Affiliations: Department of Medical Biochemistry, Faculty of Medicine and Life Sciences, University of Tampere Medical School, 33014 Tampere, Finland
- Published online on: November 17, 2017 https://doi.org/10.3892/br.2017.1020
-
Pages:
65-68
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Abstract
Cell surface heparan sulfate (HS) proteoglycans interact with other extracellular matrix (ECM) components, and HS‑binding regions are present in ECM proteins such as fibronectin and fibrillin. Because of their previously established role in susceptibility to intracranial aneurysms, the authors sought to determine whether polymorphisms of fibronectin (FN1, rs2289202) and fibrillin 2 (FBN2, rs331069) associate with selected cardiovascular risk factors and events in the TAMRISK study. A 50‑year‑old Finnish cohort of 810 subjects of whom 340 had diagnosed hypertension was analyzed. Samples were genotyped for FN1 rs2289202 and FBN2 rs331069 polymorphisms. Incidence of myocardial infarction (I21‑I22), transient cerebral ischemic attacks (TIA, G45) and cerebrovascular diseases (I60‑I69) were followed up until the subjects were on the average 60 years old. Subjects with FN1 rs2289202 (G>A) minor genotype AA had significantly more cerebrovascular disease than those with the G allele [P<0.001, odds ratio (OR), 8.73; confidence index (CI), 2.79‑27.31], although those with the A allele had lower body mass index (P=0.008). Subjects with fibrillin rs331069 (T>C) minor genotype CC had more atherothrombotic disease (P=0.012, OR, 3.16; CI, 1.29‑7.71), as measured by combined myocardial infarction and TIA, than those with the T allele. The gene polymorphisms for fibronectin and fibrillin 2 appear to associate with vascular disease.
View References
1
|
Theocharis AD, Skandalis SS, Gialeli C and
Karamanos NK: Extracellular matrix structure. Adv Drug Deliv Rev.
97:4–27. 2016. View Article : Google Scholar : PubMed/NCBI
|
2
|
Gallagher J: Fell-Muir Lecture: Heparan
sulphate and the art of cell regulation: A polymer chain conducts
the protein orchestra. Int J Exp Pathol. 96:203–231. 2015.
View Article : Google Scholar : PubMed/NCBI
|
3
|
Staunton D, Millard CJ, Aricescu AR and
Campbell ID: Preparation of recombinant fibronectin fragments for
functional and structural studies. Methods Mol Biol. 522:73–99.
2009. View Article : Google Scholar : PubMed/NCBI
|
4
|
White ES and Muro AF: Fibronectin splice
variants: Understanding their multiple roles in health and disease
using engineered mouse models. IUBMB Life. 63:538–546. 2011.
View Article : Google Scholar : PubMed/NCBI
|
5
|
Astrof S and Hynes RO: Fibronectins in
vascular morphogenesis. Angiogenesis. 12:165–175. 2009. View Article : Google Scholar : PubMed/NCBI
|
6
|
Ohtsubo H, Okada T, Nozu K, Takaoka Y,
Shono A, Asanuma K, Zhang L, Nakanishi K, Taniguchi-Ikeda M, Kaito
H, et al: Identification of mutations in FN1 leading to
glomerulopathy with fibronectin deposits. Pediatr Nephrol.
31:1459–1467. 2016. View Article : Google Scholar : PubMed/NCBI
|
7
|
Putnam EA, Zhang H, Ramirez F and Milewicz
DM: Fibrillin-2 (FBN2) mutations result in the Marfan-like
disorder, congenital contractural arachnodactyly. Nat Genet.
11:456–458. 1995. View Article : Google Scholar : PubMed/NCBI
|
8
|
Putnam EA, Park ES, Aalfs CM, Hennekam RC
and Milewicz DM: Parental somatic and germ-line mosaicism for a
FBN2 mutation and analysis of FBN2 transcript levels in dermal
fibroblasts. Am J Hum Genet. 60:818–827. 1997.PubMed/NCBI
|
9
|
Kunnas T and Nikkari ST: Contribution of
syndecan-4 genetic variants to hypertension, the TAMRISK study. BMC
Res Notes. 7:8152014. View Article : Google Scholar : PubMed/NCBI
|
10
|
Ruigrok YM, Rinkel GJ, van't Slot R, Wolfs
M, Tang S and Wijmenga C: Evidence in favor of the contribution of
genes involved in the maintenance of the extracellular matrix of
the arterial wall to the development of intracranial aneurysms. Hum
Mol Genet. 15:3361–3368. 2006. View Article : Google Scholar : PubMed/NCBI
|
11
|
Määttä KM, Nikkari ST and Kunnas TA:
Genetic variant coding for iron regulatory protein HFE contributes
to hypertension, the TAMRISK study. Medicine (Baltimore).
94:e4642015. View Article : Google Scholar : PubMed/NCBI
|
12
|
Lewis CM: Genetic association studies:
Design, analysis and interpretation. Brief Bioinform. 3:146–153.
2002. View Article : Google Scholar : PubMed/NCBI
|
13
|
Burns JD, Rabinstein AA, Roger VL, Stead
LG, Christianson TJ, Killian JM and Brown RD Jr: Incidence and
predictors of myocardial infarction after transient ischemic
attack: A population-based study. Stroke. 42:935–940. 2011.
View Article : Google Scholar : PubMed/NCBI
|
14
|
Olivieri J, Smaldone S and Ramirez F:
Fibrillin assemblies: Extracellular determinants of tissue
formation and fibrosis. Fibrogenesis Tissue Repair. 3:242010.
View Article : Google Scholar : PubMed/NCBI
|
15
|
Barth AS and Tomaselli GF: Gene scanning
and heart attack risk. Trends Cardiovasc Med. 26:260–265. 2016.
View Article : Google Scholar : PubMed/NCBI
|