Background
Methods
Patients
Clinical Definitions
Genotyping of SNPs
Gene | Location | Variable sites (a) | SNP locationb
| Primers |
---|---|---|---|---|
IL1B
| 2q14 | rs1143627 (−31 T > C) | 112836810 | IL1b31 F 5’-CCCCTAAGAAGCTTCCACCA- 3’ |
IL1b31 R 5’-AAGAGAATCCCAGAGCAGCC- 3’ | ||||
rs16944 (−511 C > T) | 112837290 | IL1b511 F 5’-TGAGGGTGTGGGTCTCTACC- 3’ | ||
IL1b511 R 5’-TGGCTAGGGTAACAGCACCT- 3’ | ||||
IL6
| 7p21 | rs1800795 (−174 G > C) | 22727026 | IL6 F 5’-TGCACTTTTCCCCCTAGTTG- 3’ |
IL6 R 5’-GCCTCAGACATCTCCAGTCC- 3’ | ||||
IL6R
| 1q21.3 | rs2228144 | 154429203 | IL6R1 F 5’-GAGAATGCTGCCCTAATCCA- 3’ |
IL6R1 R 5’-GCATTGTCTTCCGGCTCTAC- 3’ | ||||
rs2228145 (D358A A > C) | 154454494 | IL6R2 F 5’-GAGGGGAAGGTTCCTTTGAG- 3’ | ||
IL6R2 R 5’-GAACACCACAGGGCCATC- 3’ | ||||
TNFA
| 6p21.3 | rs361525 (−238 G > A) | 31575324 | TNF238 F 5’-AATCAGTCAGTGGCCCAGAA- 3’ |
TNF238 R 5’-ATCTGGAGGAAGCGGTAGTG- 3’ | ||||
rs1800629 (−308 G > A) | 31575254 | TNF308 F 5’-GAAGCCCCTCCCAGTTCTAG- 3’ | ||
TNF308 R 5’-TCTGGGCCACTGACTGATTT- 3’ | ||||
TNFRII
| 1p36.3 | rs653667 (−24660) | 12191751 | TNFR 5’-F 5’-GAGTGCAGGCTTGAGTTTCC- 3’ |
TNFR 5’-R 5’-GTGTTGTGTGTGCCCCATG- 3’ | ||||
IL10
| 1q31-32 | rs1800872 (−592 C > A) | 206773062 | IL10-592 F 5’-TGGAAACATGTGCCTGAGAA- 3’ |
IL10-592R 5’-GAGGGGGTGGGCTAAATATC- 3’ | ||||
rs1800871 (−819 G > A) | 206773289 | IL10-819 F 5’-TGGTGTACAGTAGGGTGAGG- 3’ | ||
IL10-819 R 5’-GGGAAGTGGGTAAGAGTAGTC- 3’ | ||||
rs1800896 (−1082 A > G) | 206773552 | IL10-1082 F 5’-CAACTGGCTCCCCTTACCTT- 3’ | ||
IL10-1082 R 5’-ATGGAGGCTGGATAGGAGGT- 3’ | ||||
TLR2
| 4q32 | rs4696480 | 153685974 | TLR2 F 5’-CTTGGGTGCTGCTGTAACAA- 3’ |
TLR2 R 5’-TGTTATCACCAAGGGAGCAG- 3’ | ||||
TLR4
| 9q32-33 | rs4986790 (Asp299Gly) | 117713024 | TLR4-299 F 5’-CTCTAGAGGGCCTGTGCAAT- 3’ |
TLR4-299 R 5’-TCAATGTGGGAAACTGTCCA- 3’ | ||||
rs4986791 (Thr399Ile) | 117713324 | TLR4-399 F 5’-CAACAAAGGTGGGAATGCTT- 3’ | ||
TLR4-399 R 5’-TCAAATTGGAATGCTGGAAA- 3’ | ||||
TIMP1
| Xp11.3 | rs2070584 | 47587120 | TIMP1 F 5’-CAACAGCAGCAATGGTCACT- 3’ |
TIMP1 R 5’-CTGGCAAGATGTGTGAATGG- 3’ | ||||
TIMP2
| 17q25 | rs2277698 | 78870935 | TIMP2 F 5’-TCCTCCTCCTTGTCTTTCCA- 3’ |
TIMP2 R 5’-TAGGAACAGCCCCACTTCTG- 3’ | ||||
MMP9
| 20q11.2-13.1 | rs3918242 (−1562C > T) | 46007337 | MMP9 F 5’-5’- GCCTGGCACATAGTAGGCCC-3’ |
MMP9 R 5’-5’- CTTCCTAGCCAGCCGGCATC-3’ |
Direct sequencing of controls
Identification of AIMs
Analysis
Results
Sociodemographic data and maternal ancestry
Variablesa
| Control (n = 201) | PTL (n = 136) | PPROM (n = 65) |
p (Control vs. PTL) |
p (Control vs. PPROM) |
---|---|---|---|---|---|
Age (years) | 23.9 (±6.1) | 22.8 (±6.3) | 26.2 (±6.2) | ||
GA at delivery (days) | 278 (273–284) | 251 (236–260) | 247 (238–254) |
p < 0.001 |
p < 0.001 |
GA at PTL/PPROM (days) | 241 (224–250) | 244 (230–251) | |||
Marital status | |||||
Single | 21.1 % (42/199) | 27.6 % (35/127) | 19.7 % (12/61) | NS | NS |
Married | 78.9 % (157/199) | 72.4 % (92/127) | 80.3 % (49/61) | ||
Self-reported ethnicity | |||||
White | 52.3 % (104/199) | 62.7 % (84/134) | 60 % (39/65) | NS | NS |
Non-white | 47.7 % (95/199) | 37.3 % (50/134) | 40 % (26/65) | ||
Parity | |||||
Primiparous | 48.5 % (97/200) | 46.3 % (62/134) | 36.9 % (24/65) | NS | NS |
Multiparous | 51.5 % (103/200) | 53.7 % (72/134) | 63.1 % (41/65) | ||
Smoking habits | |||||
Yes | 11.9 % (24/201) | 23.5 % (31/132) | 21.5 % (14/65) |
p = 0.007 | NS |
No | 88.1 % (177/201) | 76.5 % (101/132) | 78.5 % (51/65) | ||
Years of study | |||||
Up until 9 years | 23.8 % (45/189) | 25.6 % (32/125) | 21 % (13/62) | NS | |
9 to 12 years | 70.4 % (133/189) | 72 % (90/125) | 75.8 % (47/62) | NS | |
More than 12 years | 5.8 % (11/189) | 2.4 % (3/125) | 3.2 % (2/62) | ||
Previous PPROM | |||||
Yes | - | 20.8 % (15/72) | 24.4 % (10/41) | ||
No | 100 % (102/102) | 79.2 % (57/72) | 75.6 % (31/41) | ||
Previous PTL | |||||
Yes | - | 43.1 % (31/72) | 29.3 % (12/41) | ||
No | 100 % (102/102) | 56.9 % (41/72) | 70.7 % (29/41) | ||
Abortion | |||||
Yes | 24.8 % (28/113) | 34.7 % (25/72) | 31.7 % (13/41) | NS | NS |
No | 75.2 % (85/113) | 65.3 % (47/72) | 68.3 % (28/41) | ||
Family history PTL/PPROM | |||||
Yes | 23.3 % (24/127) | 46.6 % (62/133) | 43.1 % (28/65) |
p < 0.001 |
p < 0.001 |
No | 76.7 % (103/127) | 53.4 % (71/133) | 56.9 % (37/65) |
Variablesa
| Control group (n = 201) | PTL group (n = 88) | PPROM group (n = 44) |
p (Control vs. PTL) |
p (Control vs. PPROM) |
---|---|---|---|---|---|
Weight | 3210 (2971–3503) | 2552.5 (2210–3000) | 2255 (1909–2499) |
p < 0.001 |
p < 0.001 |
Gender | |||||
Female | 49.3 % (99/201) | 51.1 % (45/88) | 43.2 % (19/44) | ||
Male | 50.7 % (102/201) | 48.8 % (43/88) | 56.8 % (25/44) | ||
Apgar | |||||
1 | 8 (8–9) | 8 (7–9) | 8 (7–8) | NS |
p < 0.001 |
5 | 9 (9–10) | 9 (8–10) | 9 (8–9) |
p < 0.001 |
p < 0.001 |
10 | 9 (9–10) | 9 (9–10) | 9 (9–10) |
p = 0.02 | NS |
European | Amerindian | African | |
---|---|---|---|
Control (n = 201) | 0.644 (0.530–0.754)a
| 0.117 (0.082–0.190) | 0.178 (0.098–0.339)a
|
PTL (n = 127) | 0.705 (0.582–0.797)b
| 0.121 (0.074–0.182) | 0.141 (0.075–0.279)b
|
PPROM (n = 62) | 0.677 (0.570–0.800) | 0.128 (0.080–0.189) | 0.151 (0.079–0.260) |
Genotypes and haplotypes in mothers and babies
TLR2
|
TNFA-238
| ||||
---|---|---|---|---|---|
Mothers | A | T | Mothers | A | G |
Control (n = 201) | 0.408ª | 0.592 | Control (n = 201) | 0.065ª | 0.935 |
PTL (n = 136) | 0.423 | 0.577 | PTL (n = 136) | 0.044 | 0.956 |
PPROM (n = 63) | 0.548b
| 0.452 | PPROM (n = 64) | 0.008b
| 0.992 |
IL10-592
|
IL10-819
| ||||
---|---|---|---|---|---|
Babies | A | C | Babies | C | T |
Control (n = 199) | 0.369a
| 0.631 | Control (n = 199) | 0.624a
| 0.376 |
PTL (n = 92) | 0.261b
| 0.739 | PTL (n = 92) | 0.723b
| 0.277 |
PPROM (n = 40) | 0.300 | 0.700 | PPROM (n = 40) | 0.625 | 0.375 |
TNFA-308-238
| |||
---|---|---|---|
Mothers | GG | AG | GA |
Control (n = 201) | 0.838 | 0.097 | 0.065a
|
PTL (n = 136) | 0.812 | 0.154 | 0.033b
|
PPROM (n = 64) | 0.875 | 0.094 | 0.031 |
Logistic regression models
Variable | Control (n = 201) | PTL (n = 136) | OR (CI) |
p
|
---|---|---|---|---|
European ancestry | 0.64 (0.53–0.75) | 0.70 (0.58–0.80) | 13.48 (2.84–64.05) | 0.001 |
African ancestry | 0.18 (0.10–0.34) | 0.14 (0.08–0.28) | 0.10 (0.02–0.53) | 0.007 |
Smoking | 11.9 (24/201) | 23.3 (31/133) | 2.35 (1.25–4.44) | 0.008 |
Variable | Control (n = 201) | PPROM (n = 65) | OR (CI) |
p
|
---|---|---|---|---|
IL10-1082G
| 0.346 | 0.423 | 2.03 (1.06–3.92) | 0.034 |
TLR2A (rs4696480) | 0.408 | 0.548 | 2.93 (1.42–6.06) | 0.004 |
TNFA-238A
| 0.065 | 0.008 | 0.11 (0.02–0.87) | 0.036 |
Variable | Short TD (n = 87) | Longer TD (n = 79) | OR (CI) |
p
|
---|---|---|---|---|
IL1B-31 T | 0.578 | 0.447 | 2.93 (1.40–6.11) | 0.004 |
TLR4-299 G | 0.015 | 0.070 | 0.19 (0.05–0.70) | 0.013 |