Table 2 Overview of CYP3A4/5 polymorphisms effect on the response to atorvastatin

Efficacy

CYP3A4^a

*1B

rs2740574

Decreased TC^c and LDL-C^d with a significantly elevated HDL-C^b in Chilean patients (P < 0.001) [21]

Increased LDL-C^d level in American subjects (P < 0.05) [24, 34, 35]

Low LDL-C^d serum level reductions in Indians (P < 0.05) [36]

*1G

rs2242480

Decreased serum TC^c level in Chinese patients (P < 0.01) [32]

Reduced serum LDL-C^d level among Chinese patients (P = 0.049) [33]

Low (AUC_0–∞)^e for both atorvastatin and 2-OH-atorvastatin in China’s Han subjects (P < 0.05) [27]

*3 (M445T)

rs4986910

Low pretreatment serum LDL-C^d level in Americans (P = 0.032) [24, 34]

High LDL-C^d lowering response to atorvastatin in Americans; however, it failed to reach statistical significance [24, 34]

*16 (T185S)

rs12721627

More than 60% reduced functional activity for atorvastatin (in vitro study). Further research is necessary to investigate the clinical relevance [29]

*17 (189F/S)

rs4987161

Increased HDL-C^b level after atorvastatin therapy in Indians (P < 0.05) [31]

*22

rs35599367

Reduced 2-OH-atorvastatin/atorvastatin (AUC_0–∞)^e ratio in Finnish subjects (P < 0.001) [37]

CYP3A5^a

*3

rs776746

Low serum TC^c and LDL-C^d levels in Europeans (Caucasian subjects) (P < 0.05) [24, 25, 35]

Decreased LDL-C^d, TC^c, and TG^f serum levels in Greek subjects (P < 0.05) [38]

*3A

*1D

C31611T

rs17161788

A slight decline in serum TC^c and LDL-C^d in non-Afro-Brazilians (P < 0.05) [35, 39]

*3C

A6986G

rs776746

Safety

CYP3A4^a

*1B

rs2740574

A significant elevation in atorvastatin C_max^g in Chinese subjects (risk of atorvastatin intolerance due to high atorvastatin exposure) [42]

Decreased risk of statin intolerance in Dutch subjects, particularly in females and carriers of (3435T) allele of the transporter ABCB1^h (P < 0.05) [41]

*1G

rs2242480

Increased atorvastatin C_max^g in Chinese volunteers [42]

CYP3A5^a

*3

rs776746

Severe muscle damage due to the decrease in atorvastatin metabolism in Caucasian (American) subjects with European ancestry (P < 0.05) [43, 44]

Risky elevated atorvastatin C_max^g in Chinese subjects [42]

Less atorvastatin (acid form) exposure (less AUC ⁱ/DW^j and C_max^g/DW^j) than CYP3A5*1^a (p = 0.004 and 0.018, respectively) in Caucasians, Latin Americans, Blacks, and Arabs recruited in a Spanish study [26]