Table 4.
Summary of the gene polymorphisms involved in the pharmacogenetics of meglitinides.
| SNP | Study population | Associated response phenotype | Reference |
|---|---|---|---|
| SLCO1B1 | |||
| 521T>C (Val174Ala) (rs4149056) | Healthy volunteers (N = 17); a single-dose of nateglinide. | The Cmax and AUC of nateglinide were higher in the subjects with the TC and CC genotype compared to the TT genotype; the t1/2 of nateglinide in CC subjects was longer than in subjects with TT genotype. | Zhang et al, 2006 (112) |
| Healthy volunteers (N = 31); a single-dose of nateglinide. | Significant predictor of the AUC of nateglinide (a combined effect with the CYP2C9*3). | Cheng et al, 2012 (115) | |
| Healthy volunteers in two studies (N = 12) and (N = 32); a single-dose of repaglinide. | AUC of repaglinide was larger in participants with the CC genotype than in those with the TT genotype. | Kalliokoski et al, 2008 (111, 113) | |
|
| |||
| SLC30A8 | |||
| 973C>T (Arg325Trp) (rs13266634) 974G>A (Arg325Gln) (rs16889462) |
Patients with T2DM (N = 48) treated 8 weeks with repaglinide. | Better response on FINS and PINS in patients with rs13266634 CT+TT genotypes compared with CC genotype. In patients with rs16889462 GA genotype an enhanced repaglinide efficacy on FPG, PPG, and HbA1c compared with GG genotype. | Huang et al, 2010 (122) |
|
| |||
| MDR1 | |||
| 2677G>T/A (Ala893Ser/Thr) (rs2032582) | Healthy volunteers (N = 24); a single-dose of repaglinide. | AUC of repaglinide was significantly higher in subjects with the GT and TT alleles than in those with the GG and TA alleles. | Xiang et al, 2012 (118) |
|
| |||
| KCNQ1 | |||
| rs2237892 C>T rs2237895 A>C |
Patients with T2DM (N = 40) treated 8 weeks with repaglinide. | T2DM patients with the rs2237892 T allele and rs2237895 C allele were more likely to have a positive response in terms of PPG levels than T2DM patients with the rs2237892 CC and rs2237895 AA genotypes. | Dai et al, 2012 (119) |
| Patients with T2DM (N = 209) treated 8 weeks with repaglinide. | rs2237892 TT homozygotes exhibited lower 2-h glucose levels than the C allele carriers; rs2237892 C and rs2237895 C alleles were associated with larger increase in FINS and HOMA-IR. | Yu et al, 2011 (121) | |
|
| |||
| KCNJ11 | |||
| 67 A>G (Lys23Glu) (rs5219) | Patients with T2DM (N = 40) treated 8 weeks with repaglinide. | Patients with the GA or AA genotype showed higher levels of FPG, PPG, and HbA1c compared with patients with GG genotype. | Yu et al, 2010 (123) |
|
| |||
| TCF7L2 | |||
| rs290487 C>T | Patients with T2DM (N = 40) treated 8 weeks with repaglinide. | In patients with the TT genotype, a better efficacy with respect to FINS, triglycerides, and LDL-c compared to the CC or CT genotype. | Yu et al, 2010 (123) |
|
| |||
| NAMPT | |||
| −3186 C>T (rs11977021) | Patients with T2DM (N = 35) treated 8 weeks with repaglinide. | The elevated PINS in patients with CT genotypes of −3186 C/T were significantly lower than that in patients with the CC and TT genotypes. | Sheng et al, 2011 (124) |
|
| |||
| CYP2C9 | |||
| *3 (Ile359Leu) (rs1057910) | Healthy volunteers (N = 31); a single-dose of nateglinide. | Significant predictor of the AUC of nateglinide (a combined effect with the SLCO1B1 521T>C). | Cheng et al, 2012 (115) |
Cmax – maximum plasma concentration; AUC - area under the curve; t1/2 - elimination half-life; FINS - fasting insulin; PINS - postprandial insulin; FPG - fasting plasma glucose; PPG - postprandial glucose; HOMA-IR - homeostasis model of assessment - insulin resistance; LDL-c - low-density lipoprotein cholesterol.