Background
Subjects and methods
Subjects
ADIPOQ genotyping
Statistical analysis
Results
Demographic and clinical characteristics of RPL cases and control women
Casesa | Controlsa |
P
b
| |
---|---|---|---|
Age at inclusion in studyc | 31.6 ± 5.4 | 31.6 ± 4.9 | 0.94 |
Body-mass index (kg/m2)c | 26.3 ± 5.4 | 25.2 ± 4.3 | 0.004 |
Obesity [n (%)]d | 58 (19.6) | 37 (12.1) | 0.02 |
Smokers [n (%)]d | 30 (10.1) | 32 (10.8) | 0.69 |
Systolic blood pressure (mmHg)c | 114.2 ± 11.9 | 120.2 ± 17.0 | < 0.001 |
Diastolic blood pressure (mmHg)c | 72.0 ± 8.4 | 75.8 ± 9.1 | < 0.001 |
Glucose (mmol/L)c | 5.1 ± 0.9 | 5.2 ± 0.7 | 0.55 |
Menarche (years)c | 12.2 ± 1.1 | 12.8 ± 1.0 | < 0.001 |
Number of pregnanciesc | 4.2 ± 1.5 | 4.0 ± 1.1 | 0.11 |
Number of childrenc | 0.8 ± 1.1 | 4.0 ± 1.1 | < 0.001 |
Miscarriagesc | 3.6 ± 1.0 | 0.0 ± 0.1 | < 0.001 |
Association between ADIPOQ SNP and the risk of RPL
SNP | Assay ID | Position | HWE P | Alleles | Casesa | Controlsa | χ2 |
P
| aORb (95% CI) | Power |
---|---|---|---|---|---|---|---|---|---|---|
rs4632532
| C_27867233_10 | 186551682 | 0.209 | T:C |
0.351
|
0.271
|
7.035
|
0.008
|
1.46 (1.10–1.93)
|
90
|
rs16861194 | C_33187775_10 | 186559425 | 0.325 | A:G | 0.098 | 0.079 | 0.979 | 0.322 | 1.25 (0.80–1.95) | 63 |
rs17300539
| C_33187774_10 | 186559460 | 1.000 | G:A |
0.087
|
0.044
|
6.534
|
0.011
|
2.06 (1.17–3.63)
|
100
|
rs266729
| C_2412786_10 | 186559474 | 0.213 | C:G |
0.262
|
0.173
|
8.295
|
0.004
|
1.69 (1.18–2.42)
|
83
|
rs182052
| C_2412785_10 | 186560782 | 0.348 | G:A |
0.360
|
0.249
|
11.381
|
7.00 × 10
−4
|
1.70 (1.25–2.31)
|
100
|
rs16861209
| C_33187764_10 | 186563114 | 0.205 | C:A |
0.144
|
0.087
|
6.852
|
0.009
|
1.77 (1.15–2.72)
|
89
|
rs822396 | C_2910316_10 | 186566877 | 0.337 | A:G | 0.139 | 0.157 | 0.582 | 0.445 | 0.92 (0.64–1.33) | 42 |
rs7649121
| C_42772949_10 | 186568785 | 0.303 | A:T |
0.182
|
0.134
|
4.063
|
0.044
|
1.44 (1.01–2.05)
| |
rs2241766 | C_26426077_10 | 186570892 | 0.578 | T:G | 0.156 | 0.193 | 2.166 | 0.141 | 0.80 (0.57–1.12) | 62 |
rs1501299 | C_7497299_10 | 186571123 | 0.212 | C:A | 0.324 | 0.307 | 0.343 | 0.558 | 1.09 (0.83–1.43) | 54 |
rs2241767
| C_26426076_10 | 186571196 | 1.000 | A:G |
0.139
|
0.188
|
4.161
|
0.041
|
0.70 (0.49–0.98)
|
66
|
rs3774261 | C_27479710_10 | 186571559 | 0.303 | G:A | 0.462 | 0.495 | 0.989 | 0.320 | 0.87 (0.67–1.14) | 61 |
rs6773957 | C_1486294_10 | 186573705 | 0.285 | G:A | 0.506 | 0.475 | 0.951 | 0.330 | 1.13 (0.88–1.46) | 63 |
rs1063539
| C_1486290_10 | 186575392 | 0.277 | G:C |
0.147
|
0.196
|
3.898
|
0.048
|
0.70 (0.50–0.99)
|
68
|
SNP | 1/1a | 1/2a | 2/2a | ||||||
---|---|---|---|---|---|---|---|---|---|
Cases | Controls |
P
b
| Cases | Controls | OR (95% CI) | Cases | Controls | OR (95% CI) | |
rs4632532 | 141 (0.46)c | 171 (0.55) | 0.042 | 126 (0.41) | 114 (0.37) | 1.33 (0.92–1.93) |
41 (0.13)
|
25 (0.08)
|
2.03 (1.11–3.70)
|
rs1063539 | 229 (0.74) | 199 (0.64) | 0.060 |
68 (0.21)
|
95 (0.31)
|
0.63 (0.41–0.96)
| 11 (0.04) | 16 (0.05) | 0.57 (0.23–1.44) |
rs17300539 | 256 (0.83) | 283 (0.91) | 0.027 |
51 (0.17)
|
25 (0.08)
|
2.22 (1.22–4.04)
| 1 (0.003) | 1 (0.003) | 1.08 (0.07–17.41) |
rs16861209 | 229 (0.74) | 259 (0.84) | 0.032 |
69 (0.32)
|
48 (0.15)
|
1.64 (1.01–2.68)
| 10 (0.03) | 3 (0.01) | 3.87 (0.79–18.88) |
rs266729 | 187 (0.61) | 208 (0.67) | 0.079 | 88 (0.29) | 86 (0.28) | 1.14 (0.74–1.77) |
33 (0.11)
|
16 (0.05)
|
2.37 (1.09–5.18)
|
rs822396 | 233 (0.76) | 223 (0.72) | 0.650 | 66 (0.21) | 78 (0.25) | 0.81 (0.53–1.25) | 9 (0.03) | 9 (0.03) | 0.96 (0.33–2.80) |
rs1501299 | 144 (0.47) | 161 (0.52) | 0.511 | 127 (0.41) | 115 (0.37) | 1.23 (0.85–1.79) | 37 (0.12) | 34 (0.11) | 1.23 (0.69–2.17) |
rs182052 | 132 (0.43) | 174 (0.56) | 0.001 | 128 (0.42) | 119 (0.38) | 1.43 (0.94–2.17) |
48 (0.16)
|
17 (0.05)
|
3.67 (1.73–7.76)
|
rs7649121 | 222 (0.72) | 244 (0.79) | 0.190 | 57 (0.19) | 49 (0.16) | 1.30 (0.80–2.10) | 29 (0.09) | 17 (0.05) | 1.76 (0.86–3.58) |
rs2241766 | 219 (0.71) | 195 (0.63) | 0.043 | 82 (0.27) | 96 (0.31) | 0.77 (0.52–1.13) |
7 (0.02)
|
22 (0.07)
|
0.34 (0.13–0.90)
|
rs3774261 | 92 (0.30) | 93 (0.30) | 0.212 | 148 (0.48) | 127 (0.41) | 1.19 (0.76–1.86) | 68 (0.22) | 90 (0.29) | 0.78 (0.47–1.30) |
rs16861194 | 257 (0.83) | 264 (0.85) | 0.687 | 46 (0.15) | 44 (0.14) | 1.09 (0.67–1.76) | 5 (0.02) | 2 (0.01) | 2.01 (0.36–11.08) |
rs6773957 | 80 (0.26) | 88 (0.28) | 0.790 | 144 (0.47) | 144 (0.46) | 1.11 (0.73–1.69) | 84 (0.27) | 78 (0.25) | 1.18 (0.73–1.90) |
rs2241767 | 223 (0.72) | 200 (0.65) | 0.054 |
67 (0.22)
|
96 (0.31)
|
0.62 (0.42–0.93)
| 18 (0.06) | 14 (0.05) | 1.14 (0.51–2.56) |
Association of ADIPOQ polymorphisms with RPL in obese and non-obese RPL subjects
SNP | Non-obese | Obese | ||||||
---|---|---|---|---|---|---|---|---|
Controla | Casea |
P
| OR (95% CI) | Controla | Casea |
P
| OR (95% CI) | |
rs4632532 | 28.05 | 33.33 | 0.093 | 1.28 (0.96–1.71) |
12.00
|
36.17
|
0.002
|
4.15 (1.60–10.76)
|
rs1063539 |
20.45
|
14.40
|
0.028
|
0.65 (0.44–0.95)
| 23.08 | 15.85 | 0.296 | 0.63 (0.26–1.51) |
rs17300539 | 03.72 | 06.91 | 0.053 | 1.92 (0.98–3.75) | 09.26 | 17.11 | 0.202 | 2.02 (0.68–6.06) |
rs16861209 |
07.88
|
12.64
|
0.034
|
1.69 (1.03–2.76)
| 13.46 | 23.68 | 0.152 | 1.99 (0.77–5.19) |
rs266729 | 19.17 | 24.00 | 0.117 | 1.33 (0.93–1.91) | 16.67 | 30.26 | 0.125 | 2.17 (0.79–5.92) |
rs822396 | 16.09 | 14.89 | 0.647 | 0.91 (0.62–1.35) | 13.79 | 08.75 | 0.348 | 0.60 (0.20–1.76) |
rs1501299 | 29.01 | 31.86 | 0.371 | 1.14 (.085–1.54) | 32.14 | 35.56 | 0.671 | 1.16 (0.57–2.36) |
rs182052 |
26.90
|
37.50
|
0.004
|
1.63 (1.17–2.27)
|
10.71
|
31.43
|
0.005
|
3.82 (1.42–10.24)
|
rs7649121 |
13.78
|
19.19
|
0.040
|
1.49 (1.02–2.18)
|
10.71
|
26.09
|
0.046
|
2.60 (0.99–6.80)
|
rs2241766 | 20.62 | 16.09 | 0.093 | 0.74 (0.52–1.05) |
30.00
|
14.44
|
0.021
|
0.39 (0.18–0.88)
|
rs3774261 | 32.08 | 45.45 | 0.386 | 0.88 (0.65–1.18) | 46.00 | 48.68 | 0.764 | 1.11 (0.54–2.28) |
rs16861194 | 08.63 | 09.05 | 0.823 | 1.05 (0.66–1.68) | 00.00 | 07.45 | – | N/A |
rs6773957 | 49.53 | 51.50 | 0.571 | 1.08 (0.82–1.42) | 41.38 | 46.94 | 0.498 | 1.25 (0.65–2.42) |
rs2241767 | 19.82 | 15.79 | 0.125 | 0.76 (0.53–1.08) | 24.14 | 19.39 | 0.484 | 0.76 (0.35–1.65) |
Identification of ADIPOQ haplotypes associated with RPL
Haplotypeb | Frequency | Case:control frequency | χ2 |
P
| |
---|---|---|---|---|---|
Block 1 |
T A G C G C A A
|
0.433
|
0.369; 0.499
|
15.64
| 7.6 × 10−5 |
C
A G
G
A
C A
T
|
0.120
|
0.149; 0.089
|
7.86
| 5.1 × 10
−3
| |
T A G C G C G A | 0.086 | 0.082; 0.091 | 0.19 | 0.661 | |
C G G C A C A A | 0.068 | 0.076; 0.059 | 1.01 | 0.314 | |
T A
A
C G
A
A A
|
0.067
|
0.087; 0.046
|
6.27
|
0.012
| |
C A G G A C G A | 0.048 | 0.053; 0.043 | 0.52 | 0.471 | |
T A G C G A A A | 0.046 | 0.054; 0.038 | 1.23 | 0.268 | |
C A G G A C A A | 0.042 | 0.051; 0.032 | 2.14 | 0.144 | |
T A G C G C A T | 0.038 | 0.037; 0.040 | 0.04 | 0.837 | |
Block 2 | T C A G A G | 0.445 | 0.475; 0.414 | 3.71 | 0.054 |
T A A A G G | 0.291 | 0.295; 0.287 | 0.06 | 0.801 | |
G C G A G C | 0.125 | 0.119; 0.132 | 0.36 | 0.546 | |
T C A A G G | 0.029 | 0.023; 0.035 | 1.40 | 0.236 | |
G C A G A G | 0.021 | 0.015; 0.026 | 1.43 | 0.231 |