|(G;G)||less responsive to statin treatment|
|(G;T)||not as responsive to statin treatment|
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 (r2>0.90) with another, rs17244841, so practically speaking, they are equivalent to each other.
[PMID 19923996] HMGCR gene polymorphism is associated with stroke risk in the EPIC-Norfolk study
[PMID 20409966] A HMGCR polymorphism is associated with relations between blood pressure and urinary sodium and potassium ratio in the Epic-Norfolk Study
[PMID 18559695] Alternative splicing of 3-hydroxy-3-methylglutaryl coenzyme A reductase is associated with plasma low-density lipoprotein cholesterol response to simvastatin.
[PMID 18622260] Common genetic variation in six lipid-related and statin-related genes, statin use and risk of incident nonfatal myocardial infarction and stroke.
[PMID 19554360] The HMG-CoA reductase gene and lipid and lipoprotein levels: the multi-ethnic study of atherosclerosis.
[PMID 20005478] 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.