Background
Methods
Study design and subjects
SNP selection and function prediction
Genotyping
Statistical analysis
Results
Characteristics of the study population
NGT | Prediabetes | T2DM | χ2, p value | |
---|---|---|---|---|
Mean ± SD | ||||
Age (years) | 58.64 ± 11.62 | 58.73 ± 11.69 | 58.64 ± 11.82 | 0.008, 0.992a |
No. (%) | ||||
Male | 200 (48.90) | 196 (49.75) | 195 (49.12) | 0.971, 0.615 |
Income (yuans) | 6.025, 0.049 | |||
< 2000 | 203 (49.63) | 179 (45.43) | 215 (54.16) | |
≥ 2000 | 206 (50.37) | 215 (54.57) | 182 (45.84) | |
Regular exercise | 2.223, 0.329 | |||
Yes | 78 (19.07) | 86 (21.83) | 83 (20.91) | |
No | 331 (80.93) | 308 (78.17) | 314 (79.09) | |
Smoking | 1.946, 0.378 | |||
Yes | 74 (18.09) | 57 (14.47) | 70 (17.63) | |
No | 335 (81.91) | 337 (85.53) | 327 (82.37) | |
Excessive drinking | 2.460, 0.292 | |||
Yes | 36 (8.80) | 46 (11.68) | 47 (11.84) | |
No | 373 (91.20) | 348 (88.32) | 350 (88.16) | |
Hypertension | 20.666, < 0.001 | |||
Yes | 124 (30.32) | 148 (37.56) | 182 (45.84) | |
No | 285 (69.68) | 246 (62.44) | 215 (54.16) | |
BMI (kg/m2) | 43.443, < 0.001 | |||
< 25 | 298 (72.86) | 234 (59.39) | 200 (50.38) | |
≥ 25 | 111 (27.14) | 160 (40.61) | 197 (49.62) |
Associations of UCP2/UCP3 with prediabetes and T2DM
Genotype | NGT | prediabetes | T2DM | pHEW | Prediabetes | T2DM | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
OR | p | aORa | Pa | OR | p | aORa | pa | |||||
UCP2 | ||||||||||||
rs660339 | ||||||||||||
GG | 142 (35.7) | 136 (35.5) | 132 (34.1) | 0.751 | 1 | 1 | 1 | 1 | ||||
GA | 194 (48.7) | 169 (44.1) | 191 (49.4) | 0.91 (0.66,1.24) | 0.553 | 0.90 (0.66,1.24) | 0.534 | 1.06 (0.78,1.44) | 0.716 | 1.05 (0.76,1.45) | 0.763 | |
AA | 62 (15.6) | 78 (20.4) | 64 (16.5) | 1.31 (0.87,1.98) | 0.190 | 1.32 (0.87,2.00) | 0.185 | 1.11 (0.73,1.69) | 0.627 | 1.11 (0.72,1.71) | 0.641 | |
G | 478 (60.1) | 441 (57.6) | 455 (58.8) | |||||||||
Additive model (AA vs GA vs GG) | 1.11 (0.91,1.35) | 0.325 | 0.95 (0.63,1.43) | 0.798 | 1.05 (0.86,1.29) | 0.614 | 1.05 (0.86,1.29) | 0.640 | ||||
Recessive model (AA vs GA + GG) | 1.39 (0.96,2.00) |
0.082
| 1.40 (0.97,2.04) |
0.076
| 1.07 (0.73,1.57) | 0.714 | 1.08 (0.73,1.60) | 0.710 | ||||
Dominant model (GA + AA vs GG) | 1.01 (0.75,1.35) | 0.961 | 1.00 (0.75,1.35) | 0.978 | 1.07 (0.80,1.44) | 0.645 | 1.07 (0.79,1.44) | 0.686 | ||||
UCP3 | ||||||||||||
rs7930460 | ||||||||||||
AA | 195 (49.1) | 185 (48.1) | 194 (49.4) | 0.440 | 1 | 1 | 1 | 1 | ||||
AG | 171 (43.1) | 156 (40.5) | 167 (42.5) | 0.96 (0.72,1.29) | 0.795 | 0.96 (0.71,1.29) | 0.776 | 0.98 (0.73,1.31) | 0.901 | 0.99 (0.73,1.34) | 0.954 | |
GG | 31 (7.8) | 44 (11.4) | 32 (8.1) | 1.50 (0.91,2.47) | 0.116 | 1.43 (0.86,2.38) | 0.173 | 1.04 (0.61,1.77) | 0.892 | 1.02 (0.59,1.77) | 0.939 | |
A | 561 (70.7) | 526 (68.3) | 555 (70.6) | |||||||||
Additive model (GG vs AG vs AA) | 1.12 (0.90,1.39) | 0.315 | 1.10 (0.88,1.37) | 0.403 | 1.00 (0.81,1.24) | 0.985 | 1.00 (0.80,1.25) | 0.990 | ||||
Recessive model (GG vs AG + AA) | 1.52 (0.94,2.47) |
0.087
| 1.46 (0.89,2.38) | 0.134 | 1.05 (0.63,1.75) | 0.862 | 1.03 (0.60,1.75) | 0.924 | ||||
Dominant model (GG + AG vs AA) | 1.04 (0.79,1.38) | 0.765 | 1.03 (0.78,1.37) | 0.839 | 0.99 (0.75,1.31) | 0.945 | 1.00 (0.75,1.33) | 0.974 | ||||
rs15763 | ||||||||||||
GG | 281 (72.8) | 294 (77.8) | 298 (78.0) | <0.001 | 1 | 1 | 1 | 1 | ||||
GA | 39 (10.1) | 32 (8.5) | 29 (7.6) | 0.78 (0.48,1.29) | 0.336 | 0.783 (0.47,1.23) | 0.342 | 0.70 (0.42,1.17) | 0.170 | 0.67 (0.40,1.13) | 0.136 | |
AA | 66 (17.1) | 52 (13.8) | 55 (14.4) | 0.75 (0.51,1.12) | 0.163 | 0.753 (0.50,1.13) | 0.169 | 0.79 (0.53,1.16) | 0.230 | 0.77 (0.51,1.15) | 0.201 | |
G | 601 (77.8) | 620 (82.0) | 625 (81.8) | |||||||||
Additive model (AA vs GA vs GG) | 0.86 (0.71,1.04) | 0.123 | 0.86 (0.71,1.05) | 0.129 | 0.87 (0.72,1.05) | 0.142 | 0.85 (0.70,1.04) | 0.117 | ||||
Recessive model (AA vs GA + GG) | 0.77 (0.52,1.15) | 0.202 | 0.77 (0.52,1.16) | 0.210 | 0.82 (0.55,1.20) | 0.305 | 0.80 (0.53,1.20) | 0.279 | ||||
Dominant model (GA + AA vs GG) | 0.77 (0.55,1.06) | 0.111 | 0.76 (0.55,1.07) | 0.117 | 0.75 (0.54,1.05) |
0.094
| 0.73 (0.52,1.03) |
0.072
| ||||
rs1800849 | ||||||||||||
GG | 192 (48.2) | 173 (44.7) | 180 (45.7) | 0.305 | 1 | 1 | 1 | 1 | ||||
GA | 175 (44.0) | 165 (42.6) | 182 (46.2) | 1.05 (0.78,1.41) | 0.764 | 1.05 (0.78,1.41) | 0.773 | 1.11 (0.83,1.48) | 0.484 | 1.12 (0.83,1.52) | 0.447 | |
AA | 31 (7.8) | 49 (12.7) | 32 (8.1) | 1.75 (1.07,2.88) |
0.026
| 1.68 (1.02,2.78) |
0.043
| 1.10 (0.65,1.88) | 0.724 | 1.06 (0.61,1.83) | 0.842 | |
G | 559 (70.2) | 511 (66.0) | 542 (68.8) | |||||||||
Additive model (AA vs GA vs GG) | 1.22 (0.98,1.51) |
0.071
| 1.20 (0.97,1.50) | 0.098 | 1.07 (0.86,1.33) | 0.527 | 1.07 (0.85,1.33) | 0.581 | ||||
Recessive model (AA vs GA + GG) | 1.72 (1.07,2.76) |
0.025
| 1.64 (1.02,2.66) |
0.043
| 1.05 (0.63,1.75) | 0.863 | 1.00 (0.59,1.70) | 0.995 | ||||
Dominant model (AA+GA vs GG) | 1.15 (0.87,1.53) | 0.320 | 1.14 (0.86,1.52) | 0.361 | 1.11 (0.84,1.47) | 0.471 | 1.11 (0.83,1.48) | 0.473 |
Linkage disequilibrium and haplotype analysis
Haplotype | Frequency (%) | OR | p | aORa | pa |
---|---|---|---|---|---|
Prediabetes | |||||
rs643064-rs660339 | |||||
CG | 57.8 | 0.91 (0.74,1.12) | 0.393 | 0.91 (0.74,1.12) | 0.372 |
CA | 12.0 | 0.95 (0.70,1.29) | 0.736 | 0.98 (0.72,1.34) | 0.907 |
TA | 30.0 | 1.14 (0.91,1.43) | 0.241 | 1.13 (0.90,1.42) | 0.289 |
rs7930460-rs647126-rs1685356 | |||||
AAC | 18.3 | 1.04 (0.80,1.35) | 0.795 | 1.02 (0.78,1.33) | 0.865 |
AAT | 38.5 | 0.96 (0.78,1.18) | 0.721 | 0.98 (0.79,1.21) | 0.842 |
AGC | 11.8 | 0.85 (0.62,1.15) | 0.281 | 0.85 (0.63,1.16) | 0.311 |
GGC | 31.4 | 1.11 (0.89,1.38) | 0.346 | 1.10 (0.88,1.37) | 0.422 |
T2DM | |||||
rs643064-rs660339 | |||||
CG | 58.5 | 0.94 (0.77,1.15) | 0.542 | 0.94 (0.76,1.16) | 0.551 |
CA | 11.5 | 0.90 (0.66,1.23) | 0.514 | 0.90 (0.66,1.24) | 0.533 |
TA | 30.0 | 1.14 (0.92,1.43) | 0.234 | 1.15 (0.91,1.44) | 0.246 |
rs7930460-rs647126-rs1685356 | |||||
AAC | 20.3 | 1.17 (0.91,1.51) | 0.220 | 1.14 (0.87,1.48) | 0.337 |
AAT | 38.8 | 0.98 (0.80,1.20) | 0.820 | 1.01 (0.81,1.24) | 0.951 |
AGC | 11.4 | 0.82 (0.60,1.11) | 0.197 | 0.79 (0.58,1.09) | 0.148 |
GGC | 29.5 | 1.01 (0.81,1.26) | 0.900 | 1.02 (0.81,1.28) | 0.880 |
Gene-environmental interaction for prediabetes or T2DM
rs1800849 | Overweight | NGT | Prediabetes | P | OR |
---|---|---|---|---|---|
GG/GA | No | 265 (66.6) | 203 (52.5) | 1 | |
GG/GA | Yes | 102 (25.6) | 135 (34.9) |
0.001
| 1.73 (1.26,2.37) |
AA | No | 24 (6.0) | 28 (7.2) | 0.152 | 1.52 (0.86,2.71) |
AA | Yes | 7 (1.8) | 21 (5.4) |
0.002
| 3.92 (1.63,9.39) |
Interaction | 0.463 |
rs660339 | Overweight | Hypertension | NGT | T2DM | P | OR |
---|---|---|---|---|---|---|
GG/GA | No | No | 181 (45.5) | 93 (24.0) | 1 | |
GG/GA | No | Yes | 59 (14.8) | 77 (19.9) |
<0.001
| 2.54 (1.67,3.87) |
GG/GA | Yes | No | 54 (13.6) | 77 (19.9) |
<0.001
| 2.78 (1.81,4.26) |
GG/GA | Yes | Yes | 42 (10.6) | 76 (19.6) |
<0.001
| 3.52 (2.24,5.54) |
AA | No | No | 33 (8.3) | 16 (4.1) | 0.861 | 0.94 (0.49,1.80) |
AA | No | Yes | 15 (3.8) | 7 (1.8) | 0.839 | 0.91 (0.36,2.31) |
AA | Yes | No | 9 (2.3) | 21 (5.4) |
<0.001
| 4.54 (2.00,10.31) |
AA | Yes | Yes | 5 (1.3) | 20 (5.2) |
<0.001
| 7.79 (2.83,21.40) |
Interaction of rs660339-overweight |
0.021
| |||||
Interaction of rs660339-hypertension | 0.441 | |||||
Interaction of rs660339-hypertension-overweight | 0.275 |