{{Rsnum
|rsid=3846662
|Gene=HMGCR
|Chromosome=5
|position=75355259
|Orientation=minus
|GMAF=0.4155
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(C;C)
|geno2=(C;T)
|geno3=(T;T)
|Gene_s=HMGCR
}}{{ population diversity
| geno1=(C;C)
| geno2=(C;T)
| geno3=(T;T)
| CEU | 19.5 | 46.0 | 34.5
| HCB | 29.2 | 49.6 | 21.2
| JPT | 24.8 | 58.4 | 16.8
| YRI | 90.5 | 9.5 | 0.0
| ASW | 75.0 | 25.0 | 0.0
| CHB | 29.2 | 49.6 | 21.2
| CHD | 32.4 | 47.2 | 20.4
| GIH | 43.6 | 46.5 | 9.9
| LWK | 92.7 | 7.3 | 0.0
| MEX | 15.5 | 46.6 | 37.9
| MKK | 71.2 | 26.3 | 2.6
| TSI | 18.6 | 50.0 | 31.4
| HapMapRevision=28
}}
[http://www.genomeweb.com/issues/news/151152-1.html news] three SNPs that appear to have different effects in men and women [[rs3846662]] [[rs2304130]] [[rs2083637]]

[http://atvb.ahajournals.org/cgi/content/abstract/ATVBAHA.108.172288v1 journal]  LDL-[[Cholesterol]] minor allele was associated with up to 2.2-fold lower expression

{{PMID Auto GWAS
|PMID=19060911
|Trait=Cholesterol, total
|Title=Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts
|RiskAllele=G
|Pval=3E-19
|OR=0.09
|ORtxt=[NR] SD increase
|OA=1
}}

{{PharmGKB
|RSID=rs3846662
|Name_s=
|Gene_s=HMGCR
|Feature=Intron
|Evidence=PubMed ID:19060911; Web Resource:http://www.genome.gov/gwastudies/
|Annotation=GWAS results: Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts. (Initial Sample Size: 17,797 individuals; Replication Sample Size: NR); (Region: 5q13.3; Reported Gene(s): HMGCR; Risk Allele: rs3846662-G); (p-value= 0.00000000002).This variant is associated with LDL cholesterol.
|Drugs=
|Drug Classes=
|Diseases=
|Curation Level=Non-Curated
|PharmGKB Accession ID=PA164740222
}}

{{PMID Auto
|PMID=20145341
|Title=Association of the Functional Variant in the 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Gene With Low-Density Lipoprotein-Cholesterol in Japanese
}}

{{PharmGKB
|RSID=rs3846662
|Name_s=
|Gene_s=HMGCR
|Feature=Intron
|Evidence=PubMed ID:18559695
|Annotation=This intronic variant is associated with differential induction, upon simvastatin exposure, of expression of full-length HMGCR transcript versus alternatively spliced transcript lacking exon 13 (HMGCRv_1). In immortalized lymphocytes, A/A homozygotes exhibit 40% greater induction of full-length transcripts relative to A/G or G/G subjects. Conversely, A/A individuals produced 20% less alternatively spliced HMGCRv_1 transcript than A/G or G/G individuals. These differences may have implications for simvastatin efficacy, since increased induction of the alternatively spliced transcript is correlated with reduced percent response to simvastatin.
|Drugs=simvastatin
|Drug Classes=
|Diseases=Cardiovascular Diseases
|Curation Level=Curated
|PharmGKB Accession ID=PA161889391
}}

{{PharmGKB
|RSID=rs3846662
|Name_s=
|Gene_s=HMGCR
|Feature=Intron
|Evidence=PubMed ID:19060911; Web Resource:http://www.genome.gov/gwastudies/
|Annotation=GWAS results: Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts. (Initial Sample Size: 22,562 individuals; Replication Sample Size: NR); (Region: 5q13.3; Reported Gene(s): HMGCR; Risk Allele: rs3846662-G); (p-value= 3E-19).This variant is associated with Cholesterol, total.
|Drugs=
|Drug Classes=
|Diseases=
|Curation Level=Non-Curated
|PharmGKB Accession ID=PA164740194
}}

{{PMID Auto
|PMID=21427285
|Title=Effect of HMGCR Variant Alleles on Low-Density Lipoprotein Cholesterol-Lowering Response to Atorvastatin in Healthy Korean Subjects
}}

{{PMID Auto
|PMID=21867541
|Title=Evaluation of the global association between cholesterol-associated polymorphisms and Alzheimer's disease suggests a role for rs3846662 and HMGCR splicing in disease risk
|OA=1
}}

{{PMID Auto
|PMID=22654671
|Title=Knowledge-Driven Analysis Identifies a Gene–Gene Interaction Affecting High-Density Lipoprotein Cholesterol Levels in Multi-Ethnic Populations
|OA=1
}}

{{PMID|18802019|OA=1
}} Common SNPs in HMGCR in micronesians and whites associated with LDL-cholesterol levels affect alternative splicing of exon13.

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

{{PMID|19802338|OA=1
}} Genetic loci associated with plasma concentration of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A1, and Apolipoprotein B among 6382 white women in genome-wide analysis with replication.

{{PMID|19913121|OA=1
}} Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.

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

{{PMID|20005478|OA=1
}} The role of HMGCR alternative splicing in statin efficacy.

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

{{PMID|20832063}} Exploring genetic determinants of plasma total cholesterol levels and their predictive value in a longitudinal study.

{{GET Evidence
|impact=pathogenic
|qualified_impact=Insufficiently evaluated pathogenic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs3846662
|overall_frequency_n=6292
|overall_frequency_d=10758
|overall_frequency=0.584867
|n_genomes=47
|n_genomes_annotated=0
|n_haplomes=71
|n_articles=1
|n_articles_annotated=0
|in_gwas=Y
|in_pharmgkb=Y
|autoscore=2
|webscore=N
}}

{{PMID Auto
|PMID=24001602
|Title=HNRNPA1 regulates HMGCR alternative splicing and modulates cellular cholesterol metabolism
}}

{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | Affy GenomeWide 6}}
{{on chip | HumanOmni1Quad}}
{{on chip | Illumina Human 1M}}