Table 2.
Summary of the gene polymorphisms involved in the pharmacogenetics of thiazolidinediones.
| SNP | Study population | Associated response phenotype | Reference |
|---|---|---|---|
| PPARG | |||
| Pro12Ala (rs1801282) | Patients with T2DM (N = 198), 12-week rosiglitazone therapy. | The decrease in FPG and HbA1c levels was significantly greater in subjects with the Pro12Ala genotype, who had a significantly better drug response. | Kang et al, 2005 (63) |
|
| |||
| PGC-1α | |||
| +1302G>A (Thr394Thr) (rs2970847) +1564G>A (Gly482Ser) (rs8192678) |
Patients with T2DM (N = 41), 12-week rosiglitazone therapy. | Patients with the A or Ser variant were more likely to have a negative response; patients with Gly482Gly genotype had decreased FPG and PINS to a greater degree compared with Gly482Ser + Ser482Ser genotype. | Zhang et al, 2010 (64) |
|
| |||
| Resistin | |||
| −420 C>G (rs1862513) | Prospective study: T2DM patients treated with pioglitazone (N = 121) Retrospective study: T2DM patients treated with pioglitazone (N = 63) | The reduction of HbA1c correlated with the G/G genotype. | Makino et al, 2009 (65) |
|
| |||
| Adiponectin | |||
| 45T>G (Gly15Gly)(rs2241766) −11377C>G(rs266729) |
Patients with T2DM (N = 42) treated 12 weeks with rosiglitazone. | Attenuated effect in −11377CG +GG heterozygotes on FPG, PPG, HOMA-IR compared with CC genotype; enhanced effect in patients with −11377/45 CGTT diplotype on FPG and PPG. | Sun et al, 2008 (66) |
|
| |||
| Leptin | |||
| −2548G>A (rs7799039) | Patients with T2DM (N = 42) treated 12 weeks with rosiglitazone. | Patients with G allele had significantly lower BMI and serum leptin levels and increased FPG than patients with AA genotype. | Liu et al, 2008 (67) |
|
| |||
| TNF-alpha | |||
| −308G>A (rs1800629) | Patients with T2DM (N = 42) treated 12 weeks with rosiglitazone. | Attenuated effect in patients with GA+AA genotype on FINS compared with GG genotype. | Liu et al, 2008 (67) |
|
| |||
| CYP2C8 | |||
| *3 (Arg139Lys and Lys399Arg) (rs10509681) | Healthy volunteers (N = 31); a single-dose rosiglitazone. | Decreased mean total clearance, elimination half-lives, and plasma glucose AUC; *3 allele confers higher in vivo metabolic capacity than the wild-type *1 allele. | Kirchheiner et al, 2006 (71) |
FPG - fasting plasma glucose; PINS - postprandial insulin; PPG - postprandial glucose; HOMA-IR - homeostasis model of assessment - insulin resistance; BMI - body mass index; FINS - fasting insulin; AUC - area under the curve.