Rs17238540

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.

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.

This SNP is in tight linkage (r2>0.90) with another, rs17244841, so practically speaking, they are equivalent to each other.