Table 1 Characteristics of included studies (N = 17)*
Study ID | Author | Year | Gene Symbol | SNP Name | dbSNP ID | Study Design | Study Subjects | Control Source | Length of Follow-up | Results | Association |
|---|---|---|---|---|---|---|---|---|---|---|---|
Study 1 | Gloyn et al. [44] | 2001 | KCNJ11 | E23K | rs5219 | RCT | 363 Caucasian T2D and 307 normoglycemic control subjects | UKPDS | 1Â year | Variant allele did not significantly affect the response to SU therapy significantly | No |
Study 2 | Sesti et al. [45] | 2006 | KCNJ11 | E23K | rs5219 | RCT | 525 Caucasian T2D patients with secondary SU failure | Hospital-based | NA | Secondary SU failure, K allele vs E allele (OR = 1.45; 95% CI 1.01–2.09; P = 0.04). Adjustment for age, gender, fasting glycemia, glycosylated hemoglobin, age at diagnosis, and duration of diabetes in a logistic regression analysis did not change this association (OR = 1.69; 95% CI: 1.02–2.78; P = 0.04) | Yes |
Study 3 | Feng et al. [46] | 2008 | KCNJ11 | E23K | rs5219 | RCT | 1268 Chinese T2D patients treated with 8-week gliclazide | Hospital-based | 8 weeks | E23K variant of the KCNJ11 gene was significantly associated with decreases in FPG (P = 0.002). | Yes |
Study 4 | Holstein et al. [47] | 2009 | KCNJ11 | E23K | rs5219 | Case–control | 43 T2D patients treated with glimepiride or glibenclamide | Hospital-based | NA | E23K variant was significantly associated with increased HbA1c levels (adjusted P = 0.04) independent of age, sex, body mass index, diabetes duration and SU dose. | Yes |
Study 5 | Nikolac et al. [48] | 2009 | KCNJ11 | E23K | rs5219 | Cross-sectional | 228 Caucasian T2D patients with SU therapy | Hospital-based | NA | For KCNI11 E23K polymorphism, for different genotype groups, there were no significant differences of FPG, PPG, and HbA1c concentrations (P = 0.143, 0.675, and 0.824, respectively) | No |
Study 6 | El-sisi et al. [49] | 2011 | KCNJ11 | E23K | rs5219 | Case–control | 50 Egyptian T2D patients with secondary SU failure | Hospital-based | NA | Secondary SU failure, EK + KK vs. EE (RR = 1.65; 95% CI: 1.04–2.6; P = 0.04). | Yes |
Study 7 | Javorsky et al. [50] | 2012 | KCNJ11 | E23K | rs5219 | RCT | 55 T2D patients with 6-month treatment of gliclazide | Hospital-based | 6 months | For ΔHbA1c EK + KK vs. EE (1.15 ± 0.09 vs. 0.80 ± 0.13, P = 0.036) | Yes |
Study 7 | Javorsky et al. [50] | 2012 | KCNJ11 | E23K | rs5219 | RCT | 28 T2D patients with 6-month treatment of glimepiride | Hospital-based | 6 months | For ΔHbA1c EK + KK vs. EE (1.10 ± 0.12 vs. 1.00 ± 0.19 P = 0.676) | No |
Study 7 | Javorsky et al. [50] | 2012 | KCNJ11 | E23K | rs5219 | RCT | 14 T2D patients with 6-month treatment of glibenclamide | Hospital-based | 6 months | For ΔHbA1c EK + KK vs. EE (1.05 ± 0.11 vs. 0.98 ± 0.09 P = 0.633) | No |
Study 8 | Ragia et al. [51] | 2012 | KCNJ11 | E23K | rs5219 | Case–control | 92 T2D patients (80 glimepiride/12 gliclazide) who had experienced at least one drug-associated hypoglycemic event, while 84 T2D patients (74 glimepiride/10 gliclazide) who had never experienced a hypoglycemic event | Hospital-based | NA | KCNJ11 E23K genotype and allele frequencies were not different between hypoglycemic and non-hypoglycemic T2D patients (P = 0.35 and 0.47, respectively). In logistic regression models before and after adjustment for other risk factors (age, body mass index, sulfonylurea mean daily dose, duration of T2D, renal function and CYP2C9 genotype), KCNJ11 E23K polymorphism did not affect hypoglycemia risk | No |
Study 9 | Li et al. [52] | 2014 | KCNJ11 | E23K | rs5219 | RCT | 108 Chinese T2D patients treated with gliclazide for 16 weeks | Hospital-based | 16 weeks | Patients with the KK genotype had larger augmentations in changes (Δ) in acute insulin response (P = 0.049) and D body mass index (P = 0.003); Patients with the EK genotype had a lower variance in changes in fasting insulin levels (P = 0.049) and homeostasis model assessment of β cell function (P = 0.021) than those with the KK genotype | Yes |
Study 1 | Gloyn et al. [44] | 2001 | KCNJ11 | L270V | rs1800467 | RCT | 363 Caucasian T2D patients | UKPDS | 1Â year | Variant allele did not significantly affect the response to SU therapy significantly | No |
Study 10 | Meirhaeghe et al. [53] | 2001 | ABCC8 | Intron 15, exon 16 -3C/T | rs1799854 | Cross-sectional | 70 T2D patients with SU therapy | 3 large representative French samples (in Lille, Strasbourg, and Toulouse) participating in the risk factor surveys of the WHO-MONICA | NA | For T2D patients treated with SU agents, those subjects bearing at least one -3C allele and had fasting plasma TG concentrations 35% lower than TT homozygotes [2.20 mmol/L (1.14–4.14) for TT vs. 1.43 mmol/L (0.81–2.52) for TC + CC; P = 0.026] | Yes |
Study 11 | Zychma et al. [54] | 2002 | ABCC8 | Intron 15, exon 16 -3C/T | rs1799854 | Case–control | 68 Caucasian T2D patients who required insulin treatment and had known diabetes duration ≤ 5 years, compared to 99 Caucasian T2D patients receiving SU alone or in combination with metformin or acarbose with known diabetes duration ≥ 15 years | Hospital-based | NA | There was no significant impact of ABCC8 exon 16 -3C/T polymorphism on the early ineffectiveness of SU treatment (P = 0.4126 based on a Chi-square test) | No |
Study 5 | Nikolac et al. [48] | 2009 | ABCC8 | Intron 15, exon 16 -3C/T | rs1799854 | Cross-sectional | 228 Caucasian T2D patients with SU therapy | Hospital-based | NA | CC genotype of the ABCC8 exon 16 polymorphism had significantly lower HbA1c concentration compared to the patients with T genotype [6.9 (6.2–7.7) mmol/L vs. 8.1 (6.7–8.8) mmol/L; P = 0.009] | Yes |
Study 12 | Nikolac et al. [55] | 2012 | ABCC8 | Intron 15, exon 16 -3C/T | rs1799854 | Cross-sectional | 251 Caucasian T2D patients with SU therapy | Hospital-based | NA | Polymorphic allele carriers of the ABCC8 intron 15 -3C/T (which is 3Â bp ahead of exon 16) polymorphism were more frequent in the subgroup of patients with the TG concentration increase after 6Â months (P for genotype and allelic differences: 0.024 and 0.015, respectively) | Yes |
Study 13 | Zhang et al. [56] | 2007 | ABCC8 | A1369S | rs757110 | RCT | 115 T2D patients with gliclazide treatment for 8 weeks | Hospital-based | 8 weeks | For ΔHbA1c TG + GG vs. TT (1.60 ± 1.39 vs. 0.76 ± 1.70, P = 0.044) | Yes |
Study 3 | Feng et al. [46] | 2008 | ABCC8 | A1369S | rs757110 | RCT | 1268 Chinese T2D patients treated with 8-week gliclazide | Hospital-based | 8 weeks | Compared with TT genotype, subjects with the GG genotype had a 7.7% greater decrease in FPG (P < 0.001), an 11.9% greater decrease in 2-h plasma glucose (P = 0.003), and a 3.5% greater decrease in HbA1c (P = 0.06) | Yes |
Study 14 | Sato et al. [57] | 2010 | ABCC8 | A1369S | rs757110 | Case–control | 32 patients with T2D admitted to hospital with severe hypoglycemia and 125 consecutive T2D outpatients without severe hypoglycemia, and all of the patients were taking glimepiride or glibenclamide | Hospital-based | NA | There were no significant differences in ABCC8 A1369S genotype distribution between patients with or without severe hypoglycemia (P = 0.26). Moreover, the A1369 allele tended to be less frequent in the hypoglycemic group (31 vs. 43%; OR = 1.65; 95% CI: 0.92–2.96; P = 0.09) | No |
Study 5 | Nikolac et al. [48] | 2009 | ABCC8 | R1273R** | rs1799859 | Cross-sectional | 228 Caucasian T2D patients with SU therapy | Hospital-based | NA | GG genotype of the ABCC8 exon 31 polymorphism had significantly higher HbA1c concentration compared to the AA genotype [7.8 (6.9–8.8) mmol/L vs. 6.3 (5.7–6.8) mmol/L; P < 0.001] | Yes |
Study 12 | Nikolac et al. [55] | 2012 | ABCC8 | R1273R** | rs1799859 | Cross-sectional | 251 Caucasian T2D patients with SU therapy | Hospital-based | NA | Wile-type G allele carriers had a significantly higher TG concentration when compared with the carriers of two variant A alleles (P = 0.023) | Yes |
Study 15 | Pearson et al. [58] | 2007 | TCF7L2 | NA | rs7903146 | RCT | 901 T2D patients with SU treatment | GoDARTS | 12 months | Carriers of the risk allele were less likely to respond to SUs with an OR for failure of 1.95 (95% CI: 1.23–3.06; P = 0.005), comparing rs12255372 TT vs. GG. Including the baseline HbA1c strengthened this association (OR = 2.16, 95% CI: 1.21–3.86, P = 0.009) | Yes |
Study 16 | Schroner et al. [59] | 2011 | TCF7L2 | NA | rs7903146 | RCT | 87 T2D patients with 6-month SU treatment in addition to metformin | Hospital-based | 6 months | Reduction in HbA1c: CC vs. CT + TT is 1.16 ± 0.07 vs. 0.86 ± 0.07%, P = 0.003 Reduction in FPG: 1.57 ± 0.12 vs. 1.14 ± 0.14 mmol/L, P = 0.031) | Yes |
Study 17 | Holstein et al. [60] | 2011 | TCF7L2 | NA | rs7903146 | RCT | 189 T2D patients with 6-month SU treatment | Hospital-based | 6 months | T allele was significantly more frequent in the group of patients who failed to respond to SU (i.e., those with HbA1c ≥ 7%) (36%) than in the control (i.e., those with HbA1c < 7%) group (26%) (OR = 1.57, 95% CI: 1.01-2.45, P = 0.046) | Yes |