Background
Methods
Participants and sample collection
DNA extraction and UGT1A1 genotyping
Data analysis
Results
Clinical analysis
c.211 mutation/ABO HDN | c.211 normal /ABO HDN | P | |
---|---|---|---|
Sex | NS | ||
Male | 6(30.0) | 25(51.0) | |
Female | 14(70.0) | 24(49.0) | |
Gestational week | 39.4 ± 0.2 | 39.2 ± 0.1 | NS |
Birth weight (kg) | 3.3 ± 0.08 | 3.2 ± 0.06 | NS |
Peak serum bilirubin levels (umol/L) | |||
TBIL | 404(219–556) | 315(146–585) | 0.028 |
IBIL | 380(201–528) | 303(129–552) | 0.037 |
DBIL | 14 (5.0–69) | 12(3–35) | NS |
Feeding | NS | ||
Breast fed | 3(15.0) | 11(22.4) | |
Breast and formula | 2(10.0) | 9(18.4) | |
Formula | 14(70.0) | 20(40.8) | |
Unknown | 1(5.0) | 9(18.4) | |
Delivery method | NS | ||
Vaginal | 7(35.0) | 27(55.1) | |
Cesarean | 13(65.0) | 22(44.9) |
UGT1A1 variant results
UGT1A1 polymorphism | Location | N | Frequency | PH-Wa |
---|---|---|---|---|
TATA box (rs8175347) | promoter | 1 | ||
TA7 | 9 | 0.07 | ||
TA6 | 129 | 0.93 | ||
TA7/TA7 | 0 | 0 | ||
TA6/TA7 | 9 | 0.13 | ||
TA6/TA6 | 60 | 0.87 | ||
C.211 G > A (rs4148323) | Exon 1 | 1 | ||
A | 21 | 0.15 | ||
G | 117 | 0.85 | ||
A/A | 1 | 0.01 | ||
G/A | 19 | 0.28 | ||
G/G | 49 | 0.71 | ||
c.1091 C > T (rs34946978) | Exon 4 | 1 | ||
T | 3 | 0.02 | ||
C | 135 | 0.98 | ||
T/T | 0 | 0 | ||
C/T | 3 | 0.04 | ||
C/C | 66 | 0.96 | ||
Haplotype (rs8175347-rs4148323-rs34946978) | ||||
TA6GC | 0.76 | |||
TA6AC | 0.15 | |||
TA7GC | 0.065 | |||
TA6GT | 0.018 | |||
TA6AT | 0.0037 |
Co-inherited UGT1A1 variant on bilirubin levels in ABO HDNs
Genotypes | TBIL | IBIL | ||
---|---|---|---|---|
ORadjb (95%CI) | P | ORadjb (95%CI) | P | |
TATA box | ||||
TA6/TA6 | 0.00 | 0.57 | 0.00 | 0.58 |
TA6/TA7 | 30.0(−73.1–133.2) | 27.6(−70.4–125.5) | ||
c.211 G > A | ||||
G/G | 0.00 | 0.019 | 0.00 | 0.02 |
G/A-A/A | 78.2(14.7–141.8) | 73.3(12.8–133.7) | ||
c.1091 C > T | ||||
C/C | 0.00 | 0.16 | 0.00 | 0.14 |
C/T | 103.1(−39.8–245.9) | 103.6(−31.7–238.9) | ||
Haplotypec (Frequency) | ||||
TA6GC(75.85%) | 0.00 | 0.00 | ||
TA6AC(16.53%) | 84.0(23.2–144.8) | 0.0092 | 79.0(21.4–136.6) | 0.0097 |
TA7GC(5.08%) | 70.4(−26.8–167.7) | 0.16 | 65.6(−26.6–157.9) | 0.17 |
TA6GT(2.12%) | 107.9(93.7–122.1) | < 0.0001 | 107.01(93.6–120.4) | < 0.0001 |
TA6AT(0.42%) | 149.9(147.3–152.6) | < 0.0001 | 152.4(150.0–154.8) | < 0.0001 |
Co-inherited UGT1A1 variant on severe hyperbilirubinemia risk in ABO HDNs
Genotype | Total | TBIL > 342 umol/L | TBIL > 427umol/L | ||||
---|---|---|---|---|---|---|---|
N(%) | N(%) | ORadjb (95%CI) | P | N(%) | ORadjb (95%CI) | P | |
Model 1(n = 59) | |||||||
Wild type | 38(64.4%) | 16(57.1%) | 1.00 | 4(30.8%) | 1.00 | ||
Heterozygous mutation | 19(32.2%) | 10(35.7%) | 2.25(0.66–7.61) | 0.076 | 8(61.5%) | 8.74(1.86–41.09) | 0.008 |
Homozygous mutation | 2(3.4%) | 2(7.1%) | NA(0.00-NA) | 1(7.7%) | 15.09(0.61–375.49) | ||
Model 2(n = 59) | |||||||
Wild type | 38(64.4%) | 16(57.1%) | 1.00 | 4(30.8%) | 1.00 | ||
Heterozygous + Homozygous mutation | 21(35.6%) | 12(42.9%) | 2.72(0.82–9.03) | 0.093 | 9(69.2%) | 9.16(1.99–42.08) | 0.002 |
Halplotype (Frequency) | |||||||
TA6GC(75.89%) | 1.00 | 1.00 | |||||
TA6AC(16.58%) | 3.46(0.97–12.39) | 0.062 | 9.41(1.80–49.26) | 0.011 | |||
TA7GC(5.08%) | 2.57(0.37–17.89) | 0.35 | 8.18(0.80–83.65) | 0.083 | |||
TA6GT(2.17%) | 2.38(0.12–48.13) | 0.57 | 10.64(0.44–254.56) | 0.15 | |||
Otherc | – | – | – | – |