| Autor: |
Fairoozy, RH, Cooper, J, White, J, Giambartolomei, C, Folkersen, L, Wannamethee, SG, Jefferis, BJ, Whincup, P, Ben-Shlomo, Y, Kumari, M, Kivimaki, M, Wong, A, Hardy, R, Kuh, D, Gaunt, TR, Casas, JP, McLachlan, S, Price, JF, Hingorani, A, Franco-Cereceda, A, Grewal, T, Kalea, AZ, Humphries, SE, UCLEB consortium |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| ISSN: |
1879-1484 |
| Popis: |
BACKGROUND AND AIMS: Annexin-A2 (AnxA2) is an endogenous inhibitor of proprotein convertase subtilisin/kexin type-9 (PCSK9). The repeat-one (R1) domain of AnxA2 binds to PCSK9, blocking its ability to promote degradation of low-density lipoprotein cholesterol-receptors (LDL-R) and thereby regulate low-density lipoprotein cholesterol (LDL-C) levels. Here we identify variants in ANXA2 influencing LDL-C levels and we determine the molecular mechanisms of their effects. RESULTS: The ANXA2 single nucleotide polymorphism (SNP) genotype-phenotype association was examined using the Second-Northwick-Park Heart Study (NPHSII) (n∼2700) and the UCL-LSHTM-Edinburgh-Bristol (UCLEB) consortium (n∼14,600). The ANXA2-R1 domain coding-SNP rs17845226 (V98L) associated with LDL-C, homozygotes for the minor allele having ≈18.8% higher levels of LDL-C (p = 0.004), and higher risk of coronary heart disease (CHD) (p = 0.04). The SNP is in modest linkage disequilibrium (r(2) > 0.5) with two intergenic SNPs, rs17191344 and rs11633032. Both SNPs showed allele-specific protein binding, and the minor alleles caused significant reduction in reporter gene expression (≈18%, p |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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