Table 5.
Association between One Carbon Metabolism-Related Genetic Polymorphisms and Diabetes-Related Outcomes
| Variable | n | Relative Risk for Metabolic Syndrome (N=935) |
n | Mean Difference in Waist Circumference (N=1458) |
Relative Risk for Diabetes (N=1458) |
GMR for HOMA2-IR (N=1458) |
|---|---|---|---|---|---|---|
| Total | 935 | 1458 | ||||
| CBS (rs12482221) | ||||||
| AA | 365 | 1.00(Reference) | 558 | 0.00(Reference) | 1.00 (Reference) | 1.00 (Reference) |
| AG | 409 | 1.02(0.81, 1.29) | 658 | −0.51 (−2.36, 1.33) | 1.10 (0.81, 1.51) | 0.99 (0.91, 1.07) |
| GG | 161 | 1.24(0.93, 1.66) | 242 | −3.28 (−5.82, −0.74) | 1.03 (0.67, 1.57) | 0.99 (0.89, 1.11) |
| SHMT1 (rs12952556) | ||||||
| AA | 637 | 1.00(Reference) | 1002 | 0.00(Reference) | 1.00 (Reference) | 1.00 (Reference) |
| AG | 269 | 1.02(0.81, 1.28) | 410 | 0.97(−0.91, 2.86) | 1.03 (0.75, 1.43) | 1.03 (0.95, 1.12) |
| GG | 29 | 1.07(0.59, 1.93) | 46 | 2.08(−2.72, 6.87) | 0.64 (0.22, 1.82) | 1.01 (0.82, 1.24) |
| SHMT1 (rs2273027) | ||||||
| AA | 286 | 1.00(Reference) | 454 | 0.00(Reference) | 1.00 (Reference) | 1.00 (Reference) |
| AG | 463 | 0.89(0.71, 1.11) | 732 | 0.24(−1.68, 2.16) | 1.24 (0.87, 1.78) | 1.05 (0.97, 1.14) |
| GG | 186 | 1.06(0.79, 1.42) | 272 | 1.19(−1.33, 3.71) | 0.93 (0.57, 1.51) | 1.08 (0.96, 1.20) |
| PEMT (rs4646371) | ||||||
| GG | 360 | 1.00(Reference) | 584 | 0.00(Reference) | 1.00 (Reference) | 1.00 (Reference) |
| GA | 452 | 1.12(0.88, 1.43) | 681 | 1.92(0.13, 3.71) | 1.07 (0.80, 1.44) | 1.00 (0.92, 1.08) |
| AA | 123 | 1.37(1.02, 1.85) | 193 | 2.51(−0.14, 5.17) | 1.21 (0.80, 1.84) | 1.01 (0.90, 1.14) |
| MTRR (rs3776464) | ||||||
| AA | 513 | 1.00(Reference) | 775 | 0.00(Reference) | 1.00 (Reference) | 1.00 (Reference) |
| AT | 358 | 0.96(0.78, 1.19) | 579 | −0.09 (−1.91, 1.74) | 1.11 (0.79, 1.55) | 1.01 (0.93, 1.09) |
| TT | 64 | 0.86(0.54, 1.36) | 104 | −0.43 (−3.89, 3.04) | 1.13 (0.61, 2.09) | 0.90 (0.77, 1.04) |
| MTRR (rs16879334) | ||||||
| CC | 514 | 1.00(Reference) | 776 | 0.00(Reference) | 1.00 (Reference) | 1.00 (Reference) |
| CG | 357 | 0.97(0.79, 1.19) | 578 | −0.22 (−2.05, 1.60) | 1.11 (0.79, 1.56) | 1.01 (0.93, 1.09) |
| GG | 64 | 0.86(0.54, 1.36) | 104 | −0.50 (−3.96, 2.96) | 1.13 (0.61, 2.09) | 0.90 (0.77, 1.04) |
| MTHFR (rs1801131) | ||||||
| CC | 586 | 1.00(Reference) | 943 | 0.00(Reference) | 1.00 (Reference) | 1.00 (Reference) |
| CT | 306 | 0.99(0.80, 1.24) | 449 | 0.73(−1.14, 2.59) | 0.80 (0.57, 1.13) | 1.01 (0.93, 1.09) |
| TT | 43 | 0.71(0.37, 1.37) | 66 | 2.03(−2.16, 6.22) | 0.72 (0.28, 1.80) | 1.12 (0.93, 1.34) |
| MTHFR (rs1801133) | ||||||
| AA | 473 | 1.00(Reference) | 748 | 0.00(Reference) | 1.00 (Reference) | 1.00 (Reference) |
| AC | 394 | 1.08(0.89, 1.33) | 599 | −1.03 (−2.79, 0.73) | 0.94 (0.69, 1.28) | 0.95 (0.88, 1.03) |
| CC | 68 | 0.87(0.56, 1.34) | 111 | −2.34 (−5.61, 0.93) | 0.83 (0.47, 1.46) | 0.98 (0.85, 1.13) |
| MTHFR (rs2274976) | ||||||
| GG | 790 | 1.00(Reference) | 1235 | 0.00(Reference) | 1.00 (Reference) | 1.00 (Reference) |
| GA/AA | 145 | 1.07(0.82, 1.40) | 223 | 1.21(−1.11, 3.52) | 0.91 (0.60, 1.37) | 1.08 (0.98, 1.20) |
| MTHFD1 (rs3818239) | ||||||
| AA | 838 | 1.00(Reference) | 1311 | 0.00(Reference) | 1.00 (Reference) | 1.00 (Reference) |
| AG/GG | 77 | 1.00(0.73,1.37) | 147 | 0.95(−1.85, 3.75) | 0.94 (0.50, 1.76) | 1.03 (0.91, 1.16) |
| MTHFD1 (rs17751556) | ||||||
| AA | 870 | 1.00(Reference) | 1362 | 0.00(Reference) | 1.00 (Reference) | 1.00 (Reference) |
| AG/GG | 97 | 0.68(0.40, 1.17) | 96 | −1.90 (−5.33, 1.53) | 0.91 (0.48, 1.70) | 0.94 (0.81, 1.09) |
| MTR (rs10495387) | ||||||
| CC | 892 | 1.00(Reference) | 1390 | 0.00(Reference) | 1.00 (Reference) | 1.00 (Reference) |
| CA/AA | 43 | 0.84(0.54, 1.32) | 68 | −0.03 (−4.01, 3.94) | 0.67 (0.30, 1.50) | 0.79 (0.66, 0.93) |
Models adjusted for age, sex and 4 population stratification PCs
Abbreviations: GMR (geometric mean ratio); HOMA2-IR (homeostasis model assessment for insulin resistance