{{Rsnum
|rsid=12654264
|Gene=HMGCR
|Chromosome=5
|position=75352778
|Orientation=plus
|GMAF=0.4164
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(A;A)
|geno2=(A;T)
|geno3=(T;T)
|Gene_s=HMGCR
}}{{ population diversity
| geno1=(A;A)
| geno2=(A;T)
| geno3=(T;T)
| CEU | 37.2 | 46.0 | 16.8
| HCB | 21.9 | 48.9 | 29.2
| JPT | 16.8 | 58.4 | 24.8
| YRI | 47.9 | 45.2 | 6.8
| ASW | 56.1 | 29.8 | 14.0
| CHB | 21.9 | 48.9 | 29.2
| CHD | 22.0 | 45.9 | 32.1
| GIH | 11.9 | 45.5 | 42.6
| LWK | 33.6 | 52.7 | 13.6
| MEX | 53.4 | 32.8 | 13.8
| MKK | 44.2 | 42.9 | 12.8
| TSI | 39.2 | 45.1 | 15.7
| HapMapRevision=28
}}{{PMID Auto GWAS
|PMID=18193044
|Trait=LDL cholesterol
|Title=Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans
|RiskAllele=T
|Pval=9.9999999999999995E-21
|OR=0.10
|ORtxt=[0.08-0.12] % SD higher
|OA=1
}}

{{omim
|id=142910
|desc=3-@HYDROXY-3-METHYLGLUTARYL-CoA REDUCTASE; HMGCR
|rsnum=12654264
}}
{{PMID|20403997}} Genetic variation in 3-hydroxy-3-methylglutaryl CoA reductase modifies the chemopreventive activity of statins for colorectal cancer by Lipkin SM, Chao EC, Moreno V, Rozek LS, Rennert H, Pinchev M, Dizon D, Rennert G, Kopelovich L, Gruber SB in Cancer Prev Res (Phila Pa). 2010 May;3(5):597-603.

The above study shows that genotyping for HMGCR rs1265464 may help identify the subset of individuals who are most likely to achieve a CRC risk reduction and cholesterol lowering with [[statin]]s. Compared with individuals not taking statins, the unadjusted odds ratio of [[colorectal cancer]] among [[rs12654264]](A;A) statin users was 0.3 (CI: 0.18-0.51) and among [[rs12654264]](T;T) statin users, 0.66 (CI: 0.41-1.06, p-interaction 0.0012).

Their data may advance the development of personalized statin use for reducing the risk of cancer as well as cardiovascular disease among the approximately 25 million people currently using statins worldwide.

{{PMID Auto
|PMID=20403997
|Title=Genetic Variation in 3-Hydroxy-3-Methylglutaryl CoA Reductase Modifies the Chemopreventive Activity of Statins for Colorectal Cancer
}}
{{PMID Auto
|PMID=19773416
|Title=A gene score of nine LDL and HDL regulating genes is associated with fluvastatin-induced cholesterol changes in women
|OA=1
}}

{{PharmGKB
|RSID=rs12654264
|Name_s=noncoding SNP located in intron 12 of HMGCR IVS 12
|Gene_s=HMGCR
|Feature=
|Evidence=PubMed ID:20403997
|Annotation=Risk or phenotype-associated allele: A. Phenotype: Homozygotes of the A variant taking statins had lower odds of developing colorectal cancer than those with the TT variant, with heterozygotes showing intermediate risk. The A variant was also asssociated with lower serum LDL. Study size: 4187. Study population/ethnicity: Molecular Epidemiology of Colorectal Cancer (MECC) study, Jewish, Arab, Israel. Significance metric(s): p = 0.0012. Type of association: PD; CO.
|Drugs=pravastatin; simvastatin
|Drug Classes=HMG COA REDUCTASE INHIBITORS
|Diseases=Colorectal Neoplasms
|Curation Level=Curated
|PharmGKB Accession ID=PA165354745
}}

{{PMID Auto
|PMID=21149302
|Title=Effects of genetic variants on lipid parameters and dyslipidemia in a Chinese population
|OA=1
}}

{{PMID Auto GWAS
|PMID=21909109
|Trait=None
|Title=Large-scale genome-wide association studies in East Asians identify new genetic loci influencing metabolic traits.
|RiskAllele=T
|Pval=1E-20
|OR=2.7106
|ORtxt=[2.14-3.28] mg/dL decrease
}}
{{PMID Auto
|PMID=18802019
|Title=Common SNPs in HMGCR in micronesians and whites associated with LDL-cholesterol levels affect alternative splicing of exon13.
|OA=1
}}

{{PMID Auto
|PMID=18852197
|Title=Metabolic and cardiovascular traits: an abundance of recently identified common genetic variants.
|OA=1
}}

{{PMID Auto
|PMID=19060910
|Title=Genome-wide association analysis of metabolic traits in a birth cohort from a founder population.
|OA=1
}}

{{PMID Auto
|PMID=19148283
|Title=Genetic differences between the determinants of lipid profile phenotypes in African and European Americans: the Jackson Heart Study.
|OA=1
}}

{{PMID Auto
|PMID=19185284
|Title=Common variation in the beta-carotene 15,15'-monooxygenase 1 gene affects circulating levels of carotenoids: a genome-wide association study.
|OA=1
}}

{{PMID Auto
|PMID=19197348
|Title=Genome-wide association studies in an isolated founder population from the Pacific Island of Kosrae.
|OA=1
}}

{{PMID Auto
|PMID=19299407
|Title=Replication of genetic associations with plasma lipoprotein traits in a multiethnic sample.
|OA=1
}}

{{PMID Auto
|PMID=19435741
|Title=Common lipid-altering gene variants are associated with therapeutic intervention thresholds of lipid levels in older people.
|OA=1
}}

{{PMID Auto
|PMID=19554360
|Title=The HMG-CoA reductase gene and lipid and lipoprotein levels: the multi-ethnic study of atherosclerosis.
|OA=1
}}

{{PMID Auto
|PMID=19682379
|Title=TagSNP transferability and relative loss of variability prediction from HapMap to an admixed population.
|OA=1
}}

{{PMID Auto
|PMID=19951432
|Title=Analysis of recently identified dyslipidemia alleles reveals two loci that contribute to risk for carotid artery disease.
|OA=1
}}

{{PMID Auto
|PMID=20502693
|Title=Genetics and beyond--the transcriptome of human monocytes and disease susceptibility.
|OA=1
}}

{{PMID Auto
|PMID=20972250
|Title=Genetic loci associated with lipid concentrations and cardiovascular risk factors in the Korean population.
}}

{{GET Evidence
|impact=pathogenic
|qualified_impact=Insufficiently evaluated pathogenic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs12654264
|overall_frequency_n=49
|overall_frequency_d=128
|overall_frequency=0.382812
|n_genomes=36
|n_genomes_annotated=0
|n_haplomes=45
|n_articles=0
|n_articles_annotated=0
|in_gwas=Y
|autoscore=1
|webscore=N
}}

{{PMID Auto
|PMID=23098650
|Title=Impact of variants within seven candidate genes on statin treatment efficacy
}}

{{on chip | Affy GenomeWide 6}}