Table 2.
Significant and nominally significant pharmacogenetic interactions for TCF7L2 SNPs and hydrochlorothiazide treatment on new onset diabetes in INVEST whites
| SNP | Allele | Freq. | HWE1 | OR (95%CI) (HCTZ Treated, n=941)2 | OR (95%CI) (Not HCTZ Treated, n=494)2 | pinx3 | PACT4 |
|---|---|---|---|---|---|---|---|
| rs7917983 | T | 0.53 | 0.20 | 1.53 (1.04–2.25) | 0.48 (0.27–0.86) | 5.0×10−4 | 0.03 |
| rs4132670 | A | 0.32 | 0.73 | 1.44 (0.94–2.21) | 0.52 (0.28–0.98) | 8.0×10−4 | 0.05 |
| rs4506565* | T | 0.31 | 0.91 | 1.50 (0.98–2.29) | 0.53 (0.28–1.00) | 9.0×10−4 | 0.05 |
| rs4074720 | T | 0.54 | 0.49 | 1.31 (0.89–1.94) | 0.45 (0.25–0.82) | 0.001 | - |
| rs7901695* | C | 0.32 | 0.82 | 1.50 (0.98–2.29) | 0.52 (0.28–0.99) | 0.001 | - |
| rs7924080 | T | 0.53 | 0.62 | 1.26 (0.84–1.88) | 0.46 (0.26–0.83) | 0.002 | - |
| rs6585202 | T | 0.53 | 0.69 | 1.24 (0.83–1.85) | 0.46 (0.26–0.83) | 0.002 | - |
| rs11196174 | G | 0.26 | 1 | 1.11 (0.73–1.68) | 0.42 (0.20–0.88) | 0.004 | - |
| rs6585195 | C | 0.13 | 0.63 | 2.55 (1.45–4.49) | 0.87 (0.39–1.95) | 0.005 | - |
| rs10885399 | A | 0.21 | 0.16 | 1.87 (1.18–2.97) | 0.74 (0.37–1.51) | 0.009 | - |
| rs7903146* | T | 0.28 | 0.54 | 1.38 (0.90–2.12) | 0.62 (0.33–1.16) | 0.009 | - |
| rs4918789 | T | 0.55 | 0.01 | 0.87 (0.59–1.27) | 0.36 (0.19–0.68) | 0.01 | - |
| rs12243326* | C | 0.28 | 0.46 | 1.30 (0.84–2.00) | 0.60 (0.33–1.11) | 0.01 | - |
| rs7087006 | A | 0.55 | 0.02 | 0.86 (0.59–1.26) | 0.36 (0.19–0.68) | 0.01 | - |
| rs11196213 | T | 0.45 | 0.01 | 0.87 (0.59–1.27) | 0.36 (0.19–0.68) | 0.01 | - |
| rs12266632 | G | 0.06 | 0.62 | 2.24 (0.97–5.16) | 0.68 (0.21–2.24) | 0.02 | - |
| rs12573128 | G | 0.14 | 0.37 | 2.27 (1.32–3.92) | 1.01 (0.47–2.17) | 0.02 | - |
| rs7079711 | A | 0.20 | 1 | 1.11 (0.70–1.77) | 0.48 (0.21–1.09) | 0.03 | - |
| rs11594681 | A | 0.37 | 0.20 | 1.14 (0.78–1.68) | 0.58 (0.31–1.09) | 0.03 | - |
| rs17130192 | T | 0.08 | 0.26 | 1.39 (0.69–2.77) | 0.39 (0.11–1.38) | 0.04 | - |
| rs4081699 | G | 0.21 | 0.42 | 1.81 (1.15–2.84) | 0.84 (0.44–1.61) | 0.04 | - |
SNP indicates single nucleotide polymorphism; Freq, frequency of allele in INVEST whites; HWE, Hardy Weinberg Equilibrium p value; OR, odds ratio; 95%CI, 95% confidence interval; HCTZ, hydrochlorothiazide
Hardy Weinberg equilibrium p value using Fisher’s Exact test in whites
HCTZ treatment defined as exposure to HCTZ with any dose or duration before diagnosis of NOD. Odds ratios and 95% confidence intervals adjusted for age, gender, body mass index, average on treatment systolic blood pressure, hypercholesterolemia, history of smoking, principal components one, two, and three, trandolapril and atenolol treatment, and trandolapril, atenolol, and HCTZ treatment duration.
p value for interaction of HCTZ treatment and SNP after adjustment but before PACT correction
p value for interaction of HCTZ treatment and SNP after adjustment and correction for multiple testing using PACT
SNPs previously associated with type 2 diabetes or diabetes-related traits in genome wide association studies