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rs11591147

From SNPedia

Orientationplus
Stabilizedplus
Geno Mag Summary
(G;G) 0 normal
(G;T) 3.5 2-3 fold lower risk of heart disease
(T;T) 4.5 2-3 fold lower risk of heart disease
ReferenceGRCh38 38.1/141
Chromosome1
Position55039974
GenePCSK9
is asnp
is mentioned by
dbSNPrs11591147
ebirs11591147
HLIrs11591147
Exacrs11591147
Varsomers11591147
Maprs11591147
PheGenIrs11591147
hapmaprs11591147
1000 genomesrs11591147
hgdprs11591147
ensemblrs11591147
gopubmedrs11591147
geneviewrs11591147
scholarrs11591147
googlers11591147
pharmgkbrs11591147
gwascentralrs11591147
openSNPrs11591147
23andMers11591147
23andMe allrs11591147
SNP Nexus

SNPshotrs11591147
SNPdbers11591147
MSV3drs11591147
GWAS Ctlgrs11591147
GMAF0.008724
Max Magnitude4.5
? (G;G) (G;T) (T;T) 28
rs11591147, also known as R46L, is a SNP in the PCSK9 gene. As early as 2006, the minor rs11591147(T) allele was reported to be associated with lower LDL cholesterol levels, and most studies since have found that this also correlates to a two to three fold reduced risk for both early- and late-onset cardiovascular events and disease.

As part of a 9 SNP set studied in a meta-analysis totaling over 300,000 patients, rs11591147 was the SNP with the greatest effect on LDL-C and therefore cardiovascular risk reduction.[PMID 23083789] The set of SNPs was as follows, ordered from strongest to least effect on coronary risk, and the allele shown is the one associated with reduced LDL-C levels along with the associated (or nearby) lipid metabolism gene:

23andMe blog The T version of rs11591147 and the A version of rs28362286 have both been associated with decreased LDL levels. Each copy of these variants leads to lower LDL cholesterol.


[PMID 19773416OA-icon.png] A gene score of nine LDL and HDL regulating genes is associated with fluvastatin-induced cholesterol changes in women

GWAS snp
PMID [PMID 22331829]
Trait
Title Genetic determinants of statin-induced low-density lipoprotein cholesterol reduction: the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial.
Risk Allele
P-val 5E-9
Odds Ratio 5.0000 None
ClinVar
Risk rs11591147(T;T)
Alt rs11591147(T;T)
Reference rs11591147(G;G)
Significance Other
Disease Low density lipoprotein cholesterol level quantitative trait locus 1 Hypercholesterolemia
Variation info
Gene PCSK9
CLNDBN Low density lipoprotein cholesterol level quantitative trait locus 1 Hypercholesterolemia, autosomal dominant, 3
Reversed 0
HGVS NC_000001.10:g.55505647G>T
CLNSRC OMIM Allelic Variant
CLNACC RCV000003012.2, RCV000203182.2,



[PMID 17903299OA-icon.png] A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study.


[PMID 19060911OA-icon.png] Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts.


[PMID 19148283OA-icon.png] Genetic differences between the determinants of lipid profile phenotypes in African and European Americans: the Jackson Heart Study.


[PMID 19336475OA-icon.png] Integrated associations of genotypes with multiple blood biomarkers linked to coronary heart disease risk.


[PMID 19474294OA-icon.png] Potential etiologic and functional implications of genome-wide association loci for human diseases and traits.


[PMID 19913121OA-icon.png] Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.


[PMID 19951432OA-icon.png] Analysis of recently identified dyslipidemia alleles reveals two loci that contribute to risk for carotid artery disease.


[PMID 20018036OA-icon.png] Using a latent growth curve model for an integrative assessment of the effects of genetic and environmental factors on multiple phenotypes.


[PMID 20031607OA-icon.png] Longitudinal association of PCSK9 sequence variations with low-density lipoprotein cholesterol levels: the Coronary Artery Risk Development in Young Adults Study.


[PMID 21285406] Low-density lipoprotein cholesterol and the risk of cancer: a mendelian randomization study.


[PMID 22065156] Rosuvastatin, proprotein convertase subtilisin/kexin type 9 concentrations, and LDL cholesterol response: the JUPITER trial.


OMIM607786
Desc
Variant0006
Relatedalso


GET Evidence
PCSK9-R46L
aa_change Arg46Leu
aa_change_short R46L
impact protective
qualified_impact Moderate clinical importance, Likely protective
overall_frequency 0.0101389
summary This variant is reported to have a dominant protective effect against coronary heart disease. Carriers of this variant have about half the risk of coronary heart disease compared to non-carriers (6.3% risk in carriers vs. 11.8% risk in non-carriers).



[PMID 23220704] PCSK9 SNP rs11591147 is associated with low cholesterol levels but not with cognitive performance or non-cardiovascular clinical events in an elderly population

GWAS snp
PMID [PMID 18193044OA-icon.png]
Trait LDL cholesterol
Title Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans
Risk Allele T
P-val 1.9999999999999999E-44
Odds Ratio 0.47 [0.41-0.53] % SD lower
OMIM607786
DescPROPROTEIN CONVERTASE, SUBTILISIN/KEXIN-TYPE, 9; PCSK9
Variant
Relatedalso
[PMID 23300213OA-icon.png] PCSK9 SNP rs11591147 is associated with low cholesterol levels but not with cognitive performance or noncardiovascular clinical events in an elderly population.