Personalised medicine in hypercholesterolaemia: the role of pharmacogenetics in statin therapy

Figures & data

Figure 1. The simple schematic pathway for statin transporters. Statins undergo passive intestinal absorption and subsequently are taken up from the blood stream into the liver by members of solute carrier transporter family (SLCO1B1, SLCO1B3, SLCO2B1). Statins are metabolised by phase I and II enzymes and eliminated via efflux transporters mediated biliary excretion. Different enzymes are involved in phase I statin metabolism such as CYP3A4. Elimination of statins is carried out by members of the efflux family transporters ABCB1, ABCC2, ABCG2 or ABCB11. Statin metabolism and elimination take place primarily in the liver and to a lesser extent in the kidney.

Table 1. The most known genetic variants in statins pharmacogenetics reported on ClinVar/PharmKG.

Gene	rs Number	Effect	Drug	Outcome	References
SLCO1B1	rs4149056	c.521T>C (p.Val174Ala)	Simvastatin Rosuvastatin Pravastatin Cerivastatin	CC: higher risk of myopathy CT: intermediate risk of myopathy	[64, 68, 79, 87]
	rs4149015	c.-910G>A (upstream variant)	Pravastatin Pitavastatin	AA: decreased response AG: intermediate response	[87–89]
ABCG2	rs2231142	c.421C>A (p.Gln141Lys)	Rosuvastatin	GG: reduced response GT: intermediate response	[90,91]
HMGCR	rs17238540	g.27506T>G (Intron Variant)	Pravastatin	GG: reduced response TG: intermediate response	[92]
	rs3846662	g.23092A>G (Intron Variant)	Simvastatin Pravastatin	GG & AG: Probability of reduced response due to deletion of exon 13 of HMGCR gene	[53, 93]

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