TABLE 4.
Candidate gene variants showing a nominally significant interaction with the metformin intervention in the DPP
| SNP | Chromosome | Position (NCBI 36) | Gene | Alleles (m/M) | Interaction genotype * metformin |
Placebo |
Metformin |
Lifestyle |
|||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Observed P | Permuted P | FDR Q | HR (95% CI) | Observed P | HR (95% CI) | Observed P | HR (95% CI) | Observed P | |||||
| rs11868513 | 17 | 33126805 | HNF1B | A/G | 0.0007 | 0.001 | 0.33 | 1.69 (1.36–2.10) | 0.000002 | 0.87 (0.65–1.16) | 0.33 | 1.08 (0.79–1.47) | 0.64 |
| rs4148609 | 11 | 17441307 | ABCC8 | A/G | 0.002 | 0.002 | 0.33 | 1.24 (1.04–1.48) | 0.02 | 0.79 (0.63–0.98) | 0.03 | 1.06 (0.83–1.37) | 0.64 |
| rs11086926 | 20 | 42492111 | HNF4A | G/T | 0.002 | 0.001 | 0.33 | 0.82 (0.61–1.11) | 0.20 | 1.81 (1.35–2.43) | 0.0001 | 1.29 (0.91–1.83) | 0.15 |
| rs10213440 | 4 | 23475437 | PPARGC1A | C/T | 0.002 | 0.002 | 0.33 | 0.76 (0.59–0.97) | 0.03 | 1.31 (1.03–1.66) | 0.03 | 1.07 (0.80–1.43) | 0.65 |
| rs4424892 | 15 | 97921908 | MEF2A | G/A | 0.003 | 0.006 | 0.38 | 0.88 (0.72–1.09) | 0.24 | 1.43 (1.14–1.80) | 0.002 | 0.78 (0.58–1.05) | 0.10 |
| rs8065082 | 17 | 19405783 | SLC47A1 | T/C | 0.006 | 0.008 | 0.41 | 1.15 (0.97–1.37) | 0.11 | 0.78 (0.64–0.96) | 0.02 | 1.09 (0.86–1.38) | 0.46 |
| rs6666307 | 1 | 154719358 | MEF2D | T/A | 0.009 | 0.005 | 0.38 | 0.54 (0.26–1.09) | 0.08 | 2.15 (1.22–3.80) | 0.01 | 1.11 (0.44–2.77) | 0.83 |
| rs3792269 | 2 | 241180152 | CAPN10 | G/A | 0.01 | 0.01 | 0.41 | 1.61 (1.28–2.02) | 0.00005 | 0.95 (0.70–1.28) | 0.73 | 0.81 (0.55–1.18) | 0.27 |
| rs758027 | 12 | 1662034 | ADIPOR2 | C/T | 0.01 | 0.002 | 0.33 | 0.34 (0.15–0.75) | 0.01 | 1.31 (0.76–2.29) | 0.33 | 0.75 (0.26–2.15) | 0.59 |
| rs7124355 | 11 | 17369536 | KCNJ11 | A/G | 0.01 | 0.01 | 0.41 | 0.84 (0.68–1.04) | 0.10 | 1.25 (0.99–1.59) | 0.06 | 0.89 (0.68–1.17) | 0.41 |
| rs662301 | 6 | 160616909 | SLC22A2 | T/C | 0.02 | 0.02 | 0.47 | 0.78 (0.49–1.22) | 0.27 | 1.57 (1.09–2.27) | 0.02 | 0.60 (0.31–1.17) | 0.13 |
| rs2908289 | 7 | 44190467 | GCK | A/G | 0.02 | 0.02 | 0.47 | 0.86 (0.69–1.08) | 0.19 | 1.29 (1.02–1.64) | 0.04 | 0.97 (0.73–1.31) | 0.86 |
| rs741765 | 19 | 1172545 | STK11 | T/C | 0.02 | 0.02 | 0.47 | 1.17 (0.96–1.43) | 0.13 | 0.82 (0.64–1.04) | 0.10 | 0.95 (0.72–1.26) | 0.73 |
| rs6701920 | 1 | 159181541 | ITLN2 | A/G | 0.02 | 0.01 | 0.41 | 1.86 (1.19–2.91) | 0.01 | 0.49 (0.17–1.40) | 0.19 | 0.69 (0.27–1.78) | 0.45 |
| rs741579 | 5 | 149165563 | PPARGC1B | G/A | 0.02 | 0.01 | 0.38 | 2.41 (1.08–5.37) | 0.03 | 0.23 (0.03–1.62) | 0.14 | 0.68 (0.17–2.71) | 0.58 |
| rs4810083 | 20 | 55553677 | PCK1 | T/C | 0.03 | 0.03 | 0.53 | 1.14 (0.95–1.37) | 0.15 | 0.84 (0.69–1.02) | 0.08 | 1.14 (0.90–1.44) | 0.27 |
| rs9803799 | 1 | 56952660 | PRKAA2 | G/T | 0.03 | 0.02 | 0.49 | 1.17 (0.85–1.62) | 0.34 | 0.66 (0.43–1.02) | 0.06 | 1.13 (0.72–1.78) | 0.59 |
| rs17367421 | 1 | 153553865 | PKLR | C/G | 0.03 | 0.03 | 0.53 | 0.47 (0.23–0.96) | 0.04 | 1.21 (0.73–1.99) | 0.46 | 1.36 (0.77–2.38) | 0.29 |
| rs683369 | 6 | 160471194 | SLC22A1 | G/C | 0.03 | 0.03 | 0.53 | 0.99 (0.77–1.27) | 0.91 | 1.45 (1.12–1.88) | 0.004 | 0.82 (0.58–1.17) | 0.27 |
| rs249429 | 5 | 40817996 | PRKAA1 | C/T | 0.04 | 0.03 | 0.53 | 1.22 (1.01–1.46) | 0.04 | 0.89 (0.71–1.13) | 0.34 | 1.24 (0.97–1.59) | 0.09 |
| rs6733736 | 2 | 162704406 | GCG | G/A | 0.04 | 0.01 | 0.43 | 0.65 (0.20–2.13) | 0.48 | 3.70 (1.56–8.80) | 0.003 | 0.59 (0.08–4.45) | 0.61 |
| rs4253652 | 22 | 44947503 | PPARA | G/A | 0.04 | 0.02 | 0.47 | 0.60 (0.27–1.33) | 0.20 | 2.29 (1.10–4.76) | 0.03 | 1.07 (0.44–2.65) | 0.88 |
| rs6690158 | 1 | 145123867 | PRKAB2 | T/C | 0.04 | 0.03 | 0.53 | 0.58 (0.33–1.03) | 0.06 | 1.42 (0.85–2.36) | 0.18 | 1.56 (0.87–2.81) | 0.14 |
SNPs in or near biological candidate genes showing a nominally significant interaction with the metformin intervention in the DPP are shown. HRs are estimated for the minor allele (m) vs. the major allele (M) under an additive genetic model. Only the top SNP within each gene region is shown; the full set of results (including allele frequencies) is available in supplementary Table 2.