Supplemental Table 5. Impact of rs4149056 (V174A) on the pharmacokinetics of various statins	
Study	Patients	Treatment	Primary Endpoint(s)	Additional Finding(s)	
(143)	N=23 healthy Japanese volunteers	Pravastatin 10 mg	Patients with the compound N130D + V174A variant had reduced total and non-renal pravastatin clearance, as compared with patients with the N130D variant.	SLCO1B1, including V174A, are likely associated with altered pravastatin pharmacokinetics (PK).	
(108)	N=30 healthy white males	Pravastatin 40 mg	Pravastatin AUC and Cmax increased for V174A carriers compared to WT or N130D carriers.	SLCO1B1 variant haplotypes alter pravastatin disposition. Whereas V174A expression delayed hepatocellular uptake of pravastatin, N130D expression seemed to accelerate SLCO1B1-dependent uptake of the drug.	
(76)	N=41 healthy Finnish volunteers	Pravastatin 40 mg	Pravastatin AUC increased with V174A and
-11187G>A variant alleles compared to WT.	Carriers of the compound N130D + V174A variants, as well as carriers of the compound N130D + V174A +  -1187G>A, also had higher pravastatin AUC compared with WT.	
(82)	N=24 healthy Korean volunteers	Pitavastatin 1-8 mg	Pitavastatin AUC and Cmax increased for carriers of the compound N130D + V174A variant versus patients with WT or N130D alleles alone.	No significant differences were found according to genotype in terms of dose-normalized AUC or Cmax values of pitavastatin lactone	
(72)	N=36 white, 36 Chinese, 35 Malay, and 35 Asian-Indian subjects living in Singapore, Singapore	Rosuvastatin 40 mg	Rosuvastatin AUC’s were 2.36, 2.00, and 1.68 times higher in Chinese, Malay, and Asian-Indian subjects; respectively, compared with White subjects.	SLCO1B1 genotypes did not account for the observed PK differences between Asians and White subjects.	
(60)	N=16 healthy volunteers, including 8 carriers of an SLCO1B1 variant haplotype and 8 control subjects	Pravastatin 40 mg orally daily for three weeks	Pravastatin AUC and Cmax were significantly higher in patients with V174A alleles compared to controls. Patients with the  compound N130D + V174A variant, and  patients with the triplotype -11187G>A + N130D +  V174A, also had higher pravastatin AUC and Cmax	Despite considerably higher plasma pravastatin concentrations in carriers of an SLCO1B1 variant haplotype, there was no significant difference in the lipid-lowering efficacy of pravastatin between the variant haplotype and control groups.	
(75)	N=32 healthy Finnish volunteers	Pravastatin 40 mg and fluvastatin 40 mg	Pravastatin AUC, Cmax increased for men homozygous for V174A compared to men who were carriers for V174A or WT.  Women who were WT had significantly higher Pravastatin AUC, Cmax than men who were WT.  Fluvastatin PK did not differ between subjects with different SLCO1B1 genotypes or between the sexes.	SLCO1B1 polymorphism alters PK of pravastatin but not fluvastatin, which suggests that fluvastatin does not rely on SLCO1B1 for hepatic uptake. Patient gender may affect pravastatin PK. 	
(66)	N=4 healthy Caucasian volunteers	Simvastatin 40 mg	Simvastatin acid AUC and Cmax increased for V174A carriers vs. WT	The V174A variant may increase risk for myopathy as well as reduce lipid-lowering effects due to decreased hepatic uptake.	
(69)	N=107 healthy volunteers (69 European-American and 38 African-Americans)	Pravastatin 40 mg	Pravastatin AUC, Cmax increased in heterozygous carriers of the compound N130D + V174A variant and in N130D + V174A homozygotes	European-Americans had significantly higher pravastatin AUC and Cmax than African-Americans.	
(71)	N=38 healthy Japanese volunteers	Pitavastatin 2 mg	Pitavastatin AUC, Cmax increased for  N130D or compound N130D+ V174A heterozygotes,  and for compound N130D+ V174A homozygotes	Pitavastatin lactone PK parameters were not altered by SLCO1B1 genotype.	
(77)	N=32 healthy volunteers	Atorvastatin 20 mg and rosuvastatin 10 mg	AUC and Cmax for atorvastatin, 2-hydroxyatorvastatin, and rosuvastatin were increased in patients with the V174A variant.	Unexpectedly, SLCO1B1 polymorphism has a larger effect on the PK of atorvastatin than rosuvastatin.	
(118)	N=30 Korean volunteers	Rosuvastatin 10 mg	Rosuvastatin AUC increased for compound N130D + V174A homozygotes, compound N130D + V174A carriers, and N130D carriers compared with WT. Cmax increased for compound N130D + V174A homozygotes compared to other groups.	Rosuvastatin-lactone PK were similar among the three groups.	
(120)	N=11 healthy Korean volunteers	Pravastatin 40 mg or Pitavastatin 4 mg	Pitavastatin AUC and Cmax  increased more than pravastatin for compound N130D + V174A homozygotes compared with WT	Uptake into oocytes overexpressing the compound N130D + V174A allele was decreased for pitavastatin more so than pravastatin. Fluvastatin was unaffected.	
(78)	N=10 healthy Japanese volunteers	Pravastatin 10 mg   (+ olmesartan 10 mg)	Pravastatin PK not significantly affected for N130D homozygotes, versus carriers of the compound N130D + V174A variant and/or versus  N130D + V174A homozygotes	Co-administration of olmesartan + pravastatin did not affect PK based on SLCO1B1 genotype.	
(107)	N=16 healthy Chinese volunteers	Atorvastatin 40 mg  (+ rifampicin 600 mg)	When combined with concomitant rifampicin, Atorvastatin AUC increased among V174A carriers and WT patients compared to V174A homozygotes	Rifampicin PK not affected by variation in SLCO1B1 genotype.	
(70)	N=57 healthy Japanese male volunteers	Pravastatin	Relative bioavailability F(rel) increased for pravastatin in carriers of the compound N130D + V174A variant, and in homozygotes, versus WT.	Since compound N130D + V174A genotype alters F(rel), SLCO1B1 is one of the determinants of systemic exposure to pravastatin.	
(119)	N=18 healthy Chinese volunteers	Pitavastatin 2 mg	Pitavastatin AUC, Cmax increased with N130D carriers compared to wild type (WT).	Pitavastatin CL was reduced in N130D carriers. No differences according to genotype were observed in T1/2 and Tmax.
	
(144)	N=290 Korean volunteers	Atorvastatin 20 mg	Mean AUC of atorvastatin and 2-hydroxyatorvastatin was larger for compound N130D + V174A homozygotes (n = 3), than for N130D + V174A carriers (n = 8), and also larger than patients with WT.  No PK difference with atorvastatin lactone was found.	This study showed the compound N130D + V174A variant may be associated with individual difference in the AUC of atorvastatin.	
(7)	185 cases of rhabdomyolysis compared to 732 controls	Cerivastatin at various doses	Permutation test results suggested an association between cerivastatin-associated rhabdomyolysis and SLCO1B1 variants (P=0.002), but not CYP2C8 variants (P=0.073) or UGTs (P=0.523). The V174A allele was associated with risk of rhabdomyolysis (odds ratio: 1.89; 95% confidence interval: 1.40-2.56).	In transfected cells, V174A allele reduced cerivastatin transport by 40% compared with the reference transporter (P<0.001).