Background
Methods
Study subjects
SNP selection and genotyping
Statistical analysis
Results
Clinical and biochemical characteristics
Clinical characteristics | Controls (n = 500) | Patients (n = 500) | p-value |
---|---|---|---|
Gender (M, F) (%) | 28.8, 71.2 | 32.8, 67.2 | 0.170164:336 |
Age (yrs) (years) | 53.0 ± 8.4 | 57.2 ± 12.2 |
< 0.001
a
|
Age at diagnosis (yrs) | – | 49.4 ± 11.3 | ND |
Weight (kg) | 60.0 ± 10.0 | 67.7 ± 13.8 |
< 0.001
a
|
Waist circumference (cm) | 83.3 ± 9.4 | 89.6 ± 11.4 |
< 0.001
a
|
Waist-to-hip ratio | 0.8 ± 0.1 | 0.9 ± 0.1 |
< 0.001
a
|
BMI (kg/m2) | 24.1 ± 3.3 | 27.3 ± 5.0 |
< 0.001
a
|
SBP (mmHg) | 116.7 ± 15.4 | 134.9 ± 19.4 |
< 0.001
a
|
DBP (mmHg) | 71.7 ± 10.3 | 79.3 ± 10.4 |
< 0.001
a
|
FPG (mmol/l) | 3.9 (3.4, 4.4) | 8.4 (6.6, 12.1) |
< 0.001
b
|
HbA1c (mmol/mol) | 36.6 (34.2, 37.7) | 57.4 (48.0, 74.9) |
< 0.001
|
TC (mmol/l) | 208.4 ± 37.9 | 200.2 ± 53.3 |
< 0.001
a
|
TG (mmol/l) | 2.3 (2.0, 2.6) | 1.5 (1.1, 2.1) |
< 0.001
b
|
LDL-C (mmol/l) | 2.5 (1.8, 3.5) | 2.1 (1.2, 3.6) |
< 0.001
b
|
HDL-C (mmol/l) | 3.2 (2.6, 3.9) | 1.6 (1.1, 2.2) |
< 0.001
b
|
Analysis of association between SNPs and T2D
Gene | SNP (major/minor alleles*) | aRisk allele freq. | bRisk allele freq. | Subject | Genotype frequency, n (%) | Additive model | Dominant model | Recessive model | |||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
P unadjusted OR (95% CI) | P adjusted OR (95% CI) | P unadjusted OR (95% CI) | P adjusted OR (95% CI) | P unadjusted OR (95% CI) | P adjusted OR (95% CI) | ||||||||
A/A | A/B | B/B | |||||||||||
KCNQ1
| rs2237892 (C > T) | 0.76 | 0.71 | Patient | 285 (57.0) | 192 (38.4) | 23 (4.6) | 0.060 1.74 (0.99–3.07) |
0.020
2.02 (1.08–3.79) | 0.128 1.53 (0.88–2.66) | 0.057 1.83 (0.98–3.42) |
0.025
1.36 (1.04–1.78) |
0.018
1.43 (1.06–1.92) |
Control | 254 (50.8) | 205 (41.0) | 41 (8.2) | ||||||||||
CDKN2A/2B
| rs10811661 (T > C) | 0.68 | 0.62 | Patient | 228 (45.6) | 220 (44.0) | 52 (10.4) | 0.100 1.45 (0.93–2.27) |
0.044
1.65 (1.01–2.71) | 0.227 1.29 (0.85–1.96) | 0.105 1.46 (0.92–2.31) | 0.077 1.28 (0.97–1.69) | 0.066 1.33 (0.98–1.81) |
Control | 185 (37.0) | 248 (49.6) | 67 (13.4) | ||||||||||
SLC30A8
c
| rs13266634 (C > T) | 0.59 | 0.54 | Patient | 172 (34.4) | 242 (48.4) | 86 (17.2) |
0.040
1.51 (1.01–2.21) |
0.006
1.86 (1.19–2.90) | 0.309 1.20 (0.84–1.71) | 0.191 1.29 (0.87–1.91) |
0.008
1.48 (1.11–1.98) |
0.0003
1.81 (1.31–2.50) |
Control | 137 (27.4) | 268 (53.6) | 95 (19.0) | ||||||||||
HHEX
| rs1111875 (A > G) | 0.33 | 0.29 | Patient | 234 (46.8) | 200 (40.0) | 66 (13.2) |
0.039
1.61 (1.02–2.55) | 0.082 1.55 (0.94–2.56) | 0.260 1.16 (0.89–1.53) | 0.367 1.14 (0.85–1.54) |
0.044
1.56 (1.01–2.42) | 0.087 1.51 (0.94–2.45) |
Control | 254 (50.8) | 201 (40.2) | 45 (9.0) | ||||||||||
CDKAL1
| rs7756992 (A > G) | 0.43 | 0.40 | Patient | 156 (31.2) | 257 (51.4) | 87 (17.4) | 0.249 1.27 (0.84–1.90) | 0.107 1.44 (0.92–2.24) | 0.355 1.14 (0.85–1.52) | 0.169 1.25 (0.90–1.72) | 0.340 1.19 (0.83–1.71) | 0.182 1.30 (0.88–1.94) |
Control | 171 (34.2) | 254 (50.8) | 75 (15.0) | ||||||||||
TCF7L2
| rs7903146 (C > T) | 0.08 | 0.04 | Patient | 429 (85.8) | 67 (13.4) | 4 (0.0) | NA | NA |
0.006
1.80 (1.18–2.76) |
0.025
1.70 (1.06–2.72) | NA | NA |
Control | 456 (91.2) | 44 (8.8) | 0 (0.0) | ||||||||||
MTNR1B
| rs1387153 (C > T) | 0.44 | 0.42 | Patient | 164 (32.7) | 232 (46.3) | 104 (21.0) | 0.113 1.35 (0.93–1.97) | 0.120 1.38 (0.91–2.09) | 0.618 1.07 (0.80–1.42) | 0.757 1.05 (0.76–1.43) | 0.058 1.38 (0.98–1.92) |
0.047
1.44 (1.01–2.08) |
Control | 174 (34.8) | 231 (46.2) | 95 (19.0) | ||||||||||
UBE2E2
| rs7612463 (C > A) | 0.83 | 0.82 | Patient | 346 (69.3) | 134 (26.6) | 20 (4.0) | 0.875 0.94 (0.47–1.89) | 0.855 0.93 (0.42–2.03) | 0.890 0.95 (0.47–1.90) | 0.872 0.93 (0.43–2.03) | 0.847 0.97 (0.72–1.29) | 0.826 0.96 (0.70–1.32) |
Control | 339 (67.8) | 141 (28.2) | 20 (4.0) |
Analysis of association between SNPs and quantitative traits
Clinical characteristics | CDKN2A/2B (rs10811661) genotypes | SLC30A8 (rs13266634) genotypes | TCF7L2 (rs7903146) genotypes | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
T/T | T/C | C/C |
P
| C/C | C/T | T/T |
P
| C/C | C/T + TT |
P
| |
Number of patients | 228 | 220 | 52 | – | 172 | 242 | 86 |
–
| 429 | 71 |
–
|
Weight (kg) | 68.99 ± 13.96 | 67.42 ± 13.73 | 65.01 ± 14.28 | 0.250 | 66.38 ± 14.78 | 66.38 ± 14.78 | 66.38 ± 14.78 | 0.867 | 67.58 ± 13.60 | 68.83 ± 15.45 | 0.172 |
Waist circumference (cm) | 89.34 ± 11.32 | 89.39 ± 11.69 | 92.59 ± 11.04 |
0.007
| 89.55 ± 11.58 | 89.79 ± 10.82 | 89.87 ± 12.75 | 0.506 | 89.66 ± 11.30 | 89.84 ± 12.27 | 0.861 |
Waist-to-hip ratio | 0.89 ± 0.07 | 0.91 ± 0.08 | 0.92 ± 0.11 |
0.023
| 0.91 ± 0.07 | 0.90 ± 0.08 | 0.90 ± 0.08 | 0.263 | 0.90 ± 0.08 | 0.90 ± 0.080 | 0.334 |
BMI (kg/m2) | 27.60 ± 5.06 | 27.07 ± 4.99 | 26.82 ± 5.075 | 0.442 | 26.65 ± 5.15 | 27.62 ± 4.72 | 27.59 ± 5.38 | 0.273 | 27.27 ± 5.067 | 27.14 ± 4.71 | 0.736 |
SBP (mmHg) | 133.60 ± 19.99 | 134.21 ± 17.58 | 143.52 ± 23.29 | 0.746 | 134.94 ± 18.56 | 134.44 ± 19.30 | 136.47 ± 21.82 | 0.740 | 135.25 ± 19.64 | 132.98 ± 18.15 | 0.800 |
DBP (mmHg) | 78.84 ± 10.72 | 79.42 ± 9.87 | 80.75 ± 11.65 | 0.228 | 79.95 ± 10.16 | 78.56 ± 10.85 | 80.18 ± 9.89 | 0.348 | 79.43 ± 10.62 | 78.87 ± 9.21 | 0.469 |
FPG (mmol/l) | 9.27 (7.05, 12.49) | 8.16 (6.38, 11.88) | 7.79 (6.33, 10.68) | 0.244 | 8.33 (6.64, 11.62) | 8.49 (6.38, 12.93) | 8.77 (6.84, 11.94) | 0.164 | 8.49 (6.50, 12.25) | 8.55 (6.94, 8.55) | 0.721 |
HbA1c (mmol/mol) | 59.05 (49.70, 78.92) | 56.30 (48.6, 71.6) | 53.00 (44.82, 77.3) | 0.683 | 56.30 (48.6, 71.6) | 57.40 (49.7, 76.5) | 59.05 (48.32, 78.10) |
0.018
| 57.40 (48.60, 74.9) | 56.30 (47.50, 56.30) | 0.535 |
TC (mmol/l) | 202.96 ± 53.19 | 197.52 ± 51.12 | 195.80 ± 60.28 | 0.748 | 197.40 ± 55.56 | 199.65 ± 51.20 | 208.33 ± 55.57 | 0.853 | 200.65 ± 54.08 | 198.00 ± 49.65 | 0.592 |
TG (mmol/l) | 1.46 (1.03, 2.06) | 1.50 (1.18, 2.11) | 1.64 (1.17, 2.06) | 0.197 | 1.43 (1.02, 2.05) | 1.51 (1.14, 2.08) | 1.51 (1.18, 2.26) | 0.664 | 1.52 (1.15, 2.10) | 1.32 (1.06, 1.32) | 0.600 |
LDL-C (mmol/l) | 2.22 (1.39, 3.85) | 2.15 (1.30, 3.50) | 1.47 (1.10, 2.87) | 0.943 | 1.89 (1.34, 3.64) | 2.38 (1.22, 3.78) | 2.22 (1.37, 3.71) | 0.854 | 2.17 (1.33, 3.68) | 1.71 (1.16, 1.71) | 0.741 |
HDL-C (mmol/l) | 1.58 (1.14, 2.21) | 1.63 (1.19, 2.265) | 1.78 (1.44, 2.32) | 0.965 | 1.64 (1.17, 2.24) | 1.61 (1.19, 2.17) | 1.55 (1.14, 2.50) | 0.464 | 1.60 (1.16, 2.18) | 1.81 (1.34, 1.81) |
0.023
|