{{Rsnum
|rsid=17238540
|Gene=HMGCR
|Chromosome=5
|position=75359673
|Orientation=plus
|GMAF=0.03581
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(G;G)
|geno2=(G;T)
|geno3=(T;T)
|Gene_s=HMGCR
}}[[rs17238540]], also known as SNP 29, is located in the HMG-CoA reductase [[HMGCR]] gene. The protein encoded by this gene is the target for drugs designed to inhibit its action, in order to lower cholesterol levels. SNPs in the [[HMGCR]] gene may affect how well such drugs (typically [[statins]]) work.

In a study of ~1,500 patients treated with 40mg/d of [[pravastatin]], [[rs17238540]](G;T) heterozgyotes had a mean decrease in total cholesterol of 32.5 mg/dL (0.85 mmol/L), while the mean change for [[rs17238540]](T;T) homozygotes was 41.8 mg/dL (1.09 mmol/L), a reduction in overall efficacy of 22.3% (absolute difference, 9.3 mg/dL, CI: 3.8-14.7 mg/dL, p<.001). The drop in total cholesterol was almost completely due to the decrease in LDL cholesterol, as there was no significant difference in the change in HDL cholesterol with [[pravastatin]] between genotypes.{{PMID|15199031}}

A separate study of 1,000 Scottish individuals taking [[statins]] found that 28% of [[rs17238540]](T;T) individuals failed to reach target compared with 51% of the individuals carrying a (G) allele, yielding an adjusted odds ratio for failure of 2.93 (CI: 1.61-5.34) mmol/l, p=0.0005. Additionally, they found that heterozygotes had a 13% smaller reduction in total cholesterol (-32.3 vs. -37.1%, p=0.0081) and a 27% smaller reduction in triglycerides (-27.5 vs. -37.6%, p=0.0046), leading to their conclusion that [[rs17238540]](G;T) heterozygotes may respond less well to statin therapy in terms of lowered total cholesterol and triglycerides. {{PMID|18815589}}

This SNP is in tight linkage (r<sup>2</sup>>0.90) with another, [[rs17244841]], so practically speaking, they are equivalent to each other.

{{PMID Auto
|PMID=19923996
|Title=HMGCR gene polymorphism is associated with stroke risk in the EPIC-Norfolk study
}}

{{PharmGKB
|RSID=rs17238540
|Name_s=
|Gene_s=HMGCR
|Feature=Intron
|Evidence=PubMed ID:18815589
|Annotation=Caucasian diabetic patients treated with statins and heterozygous for this SNP (GT genotype) were less likely to reach target levels for reduction of lipid and cholesterol measurements relative to TT individuals. GT heterozygotes also had smaller overall reductions in total cholesterol and triglycerides.
|Drugs=
|Drug Classes=HMG COA REDUCTASE INHIBITORS
|Diseases=Hyperlipidemias
|Curation Level=Curated
|PharmGKB Accession ID=PA162363715
}}

{{PMID Auto
|PMID=20409966
|Title=A HMGCR polymorphism is associated with relations between blood pressure and urinary sodium and potassium ratio in the Epic-Norfolk Study
}}

{{PharmGKB
|RSID=rs17238540
|Name_s=HMGCR:SNP 29
|Gene_s=HMGCR
|Feature=Intron
|Evidence=Web Resource:http://www.pharmgkb.org/search/annotatedGene/hmgcr/variant.jsp
|Annotation=Conflicting studies, but this SNP has been associated with total cholesterol and LDL-cholesterol levels.
|Drugs=pravastatin
|Drug Classes=
|Diseases=
|Curation Level=In-Depth
|PharmGKB Accession ID=PA161145168
}}

{{PMID|18559695|OA=1
}} Alternative splicing of 3-hydroxy-3-methylglutaryl coenzyme A reductase is associated with plasma low-density lipoprotein cholesterol response to simvastatin.

{{PMID|18622260|OA=1
}} Common genetic variation in six lipid-related and statin-related genes, statin use and risk of incident nonfatal myocardial infarction and stroke.

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

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

{{PMID|20540816}} A single nucleotide polymorphism in the 3-hydroxy-3-methylglutaryl-coenzyme A reductase gene ( HMGCR) influences the serum triacylglycerol relationship with dietary fat and fibre in the European Prospective Investigation into Cancer and Nutrition in Norfolk (EPIC-Norfolk) study.

{{GET Evidence
|impact=pharmacogenetic
|qualified_impact=Insufficiently evaluated pharmacogenetic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs17238540
|overall_frequency_n=4
|overall_frequency_d=128
|overall_frequency=0.03125
|n_genomes=5
|n_genomes_annotated=0
|n_haplomes=5
|n_articles=2
|n_articles_annotated=2
|qualityscore_in_vitro=0
|in_pharmgkb=Y
|autoscore=1
|webscore=N
|summary_short=this polymorphism has effect on how strongly blood pressure reacts to the salt intake. 
}}

{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | FTDNA2}}
{{on chip | HumanOmni1Quad}}