rs11591147
| Orientation | plus |
| Stabilized | plus |
| 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 |
| Reference | GRCh38 38.1/141 |
| Chromosome | 1 |
| Position | 55039974 |
| Gene | PCSK9 |
| is a | snp |
| is | mentioned by |
| dbSNP | rs11591147 |
| dbSNP (classic) | rs11591147 |
| ClinGen | rs11591147 |
| ebi | rs11591147 |
| HLI | rs11591147 |
| Exac | rs11591147 |
| Gnomad | rs11591147 |
| Varsome | rs11591147 |
| LitVar | rs11591147 |
| Map | rs11591147 |
| PheGenI | rs11591147 |
| Biobank | rs11591147 |
| 1000 genomes | rs11591147 |
| hgdp | rs11591147 |
| ensembl | rs11591147 |
| geneview | rs11591147 |
| scholar | rs11591147 |
| rs11591147 | |
| pharmgkb | rs11591147 |
| gwascentral | rs11591147 |
| openSNP | rs11591147 |
| 23andMe | rs11591147 |
| SNPshot | rs11591147 |
| SNPdbe | rs11591147 |
| MSV3d | rs11591147 |
| GWAS Ctlg | rs11591147 |
| GMAF | 0.008724 |
| Max Magnitude | 4.5 |
| ? | (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:
- rs11591147(T), PCSK9
- rs4420638(A), APOE
- rs6511720(T), LDLR
- rs599839(G), SORT1
- rs646776(C), SORT1
- rs2228671(T), LDLR
- rs11206510(C), PCSK9
- rs4299376(T), ABCG8
- rs12916(T), HMGCR
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 19773416
] 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(A;A) Rs11591147(T;T) |
| Alt | rs11591147(A;A) Rs11591147(T;T) |
| Reference | Rs11591147(G;G) |
| Significance | Other |
| Disease | Low density lipoprotein cholesterol level quantitative trait locus 1 Hypercholesterolemia Familial hypercholesterolemia |
| Variation | info |
| Gene | PCSK9 |
| CLNDBN | Low density lipoprotein cholesterol level quantitative trait locus 1 Hypercholesterolemia, autosomal dominant, 3 Familial hypercholesterolemia |
| Reversed | 0 |
| HGVS | NC_000001.10:g.55505647G>T |
| CLNSRC | OMIM Allelic Variant UniProtKB (protein) |
| CLNACC | RCV000003012.2, RCV000203182.3, RCV000256313.2, |
[PMID 17903299] A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study.
[PMID 19060911] Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts.
[PMID 19148283] Genetic differences between the determinants of lipid profile phenotypes in African and European Americans: the Jackson Heart Study.
[PMID 19336475] Integrated associations of genotypes with multiple blood biomarkers linked to coronary heart disease risk.
[PMID 19474294] Potential etiologic and functional implications of genome-wide association loci for human diseases and traits.
[PMID 19913121] Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
[PMID 19951432] Analysis of recently identified dyslipidemia alleles reveals two loci that contribute to risk for carotid artery disease.
[PMID 20018036] Using a latent growth curve model for an integrative assessment of the effects of genetic and environmental factors on multiple phenotypes.
[PMID 20031607] 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.
[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 18193044]
|
| 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 |
[PMID 23300213] PCSK9 SNP rs11591147 is associated with low cholesterol levels but not with cognitive performance or noncardiovascular clinical events in an elderly population.
[PMID 29748315] Genetic Regulation of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Plasma Levels and Its Impact on Atherosclerotic Vascular Disease Phenotypes.
[PMID 33091218] PCSK9 rs11591147 R46L Loss-of-Function Variant Protects Against Liver Damage in Individuals with NAFLD.
