Christmas in the Heart

rs11591147 is a SNP that warms the heart. This PCSK9 gene SNP has been known since 2005 to be associated with reduced average low density lipoprotein cholesterol (LDL-C), but this year it became the poster child of a set of 9 SNPs used to tackle a key question: to reduce heart disease risk, just how early in life should we start paying attention to LDL-C levels?

The meta-analysis of over 300,000 (!) patients published by Ference et al. [PMID:23083789] concludes that a person who’s lifetime average LDL exposure was reduced by about 40 mg/dl due to one or more of these 9 SNPs has their coronary heart disease risk cut in half. Their models suggest that the earlier you experience lower LDL levels, the better. If you weren’t born with enough of the LDL-lowering variants like rs11591147(T), the sooner you lower your LDL, the better, either by changing your lifestyle (through your diet) or by taking statins. Atherosclerosis isn’t just for old folks – it’s a progressive disease that begins in childhood.

This reminds us of rs4149056, a SNPedia Top 10 SNP pick of 2010. rs4149056(C) alleles and especially rs4149056(C;C) genotypes are associated with higher risk for side effects (muscle pain and degradation) when taking the statin simvastatin. This year, the Clinical Pharmacogenomics Implementation Consortium (CPIC) issued a clinical guideline with dosing recommendations for simvastatin when rs4149056 status is available [PMID: 22617227]. Pharmacogenomics continues to be one of the areas where genomics is directly improving patient health and well-being, and that too warms our hearts.