The Relationship between the HLA-G Polymorphism and sHLA-G Levels in Parental Pairs with High-Risk Pregnancy
Abstract
:1. Introduction
2. Material and Methods
2.1. Experimental and Control Groups
2.2. Division into Groups
- Antiphospholipid syndrome (affecting 70 women with 54 partners) was diagnosed using laboratory and clinical criteria (history of autoimmune diseases, thrombotic complications, and embolic complications, as well as general obstetric history). Inclusion criteria were [13]: (1) thrombosis (meaning at least one episode of capillary thrombosis in any part of the body, venous thrombosis, or arterial thrombosis—excluding superficial venous thrombosis—as confirmed by histological examination or imaging); (2) obstetric failure (meaning at least one premature birth of a morphologically normal fetus prior to week 34 of pregnancy because of placental insufficiency, eclampsia, or preeclampsia; severe death of at least one morphologically normal fetus after week 10; or at least three spontaneous miscarriages prior to week 10 from other than anatomical causes, hormonal disorders of the mother, or chromosomal disorders of both parents); (3) laboratory criteria—specifically, lupus anticoagulant—detected in plasma at least twice (minimum of twelve weeks apart) through methods recommended by the International Society on Thrombosis and Haemostasis; mean or high levels of IgG or IgM class anticardiolipin antibodies (>40 GPL or MPL or <99th percentile) detected on at least two occasions minimum 12 weeks apart by a standardized ELISA method; or anti-β2-glycoprotein I antibodies in serum or plasma measured over the 99th percentile at least twice (minimum of twelve weeks apart).
- Severe preeclampsia (affecting 43 women with 43 partners) was diagnosed by [14]: (1) proteinuria and higher blood pressure after week 20 of pregnancy (except in cases of multifetal pregnancy or gestational trophoblastic disease) and; (2) no proteinuria in cases where the following happened for the first time after week 20: disorders of the vision, pulmonary edema, central nervous system disorders, liver disease (doubled transaminase activity), impaired renal function (creatinine over 1.1 mg/dL or doubling in creatinine in the absence of a history of kidney disease), or thrombocytopenia (blood platelet count below 100,000 per µL).
- Intrauterine growth restriction (affecting 58 women with their 58 partners) involved a fetal weight measured at the first ultrasound at the 10th percentile or lower for the gestational age, excluding causes of intrauterine growth restriction, such as smoking, alcohol consumption, diabetes, hypertension, genetic determinants, preeclampsia, uterine abnormalities, infections, renal diseases, taking medicine, autoimmune diseases, and malformations of fetal developmental.
- Recurrent spontaneous abortion (affecting 58 women with their 58 partners) involved having at least three spontaneous miscarriages in the first trimester, excluding other causes of miscarriage. Normal karyotype was determined for all couples, and health problems like thyroid and adrenal gland diseases, diabetes, infections (including herpes, syphilis, HIV, varicella, rubella, cytomegaloviral disease, toxoplasmosis, and others), anatomic abnormalities, and autoimmune diseases (presence of lupus anticoagulant, anticardiolipin antibodies, or antinuclear antibodies) were excluded.
- The control group contained 89 healthy women with their 86 partners. These women lacked significant perinatal history and had given birth at least twice after uncomplicated pregnancies. Thrombotic and embolic complications, as well as concomitant autoimmune diseases, were excluded.
2.3. Isolation of Genomic DNA from Peripheral Blood Leukocytes
2.4. Sequencing
2.5. Analysis of the −725 C>G Polymorphism in the HLA-G Promoter Region
- F 5′GAA AGT GAA ACT TAA GAG CTT TGT GAG GC 3′
- R 5′TTG GTA ACC CCT GAA TGA TCA G 3′
2.6. Determination of Serum sHLA-G Levels
2.7. Statistical Analysis
3. Results
3.1. Serum sHLA-G Levels in Women with Previous Complicated Pregnancies
3.2. Frequency of the HLA-G −725 C>G Polymorphism in Parental Pairs with Regard to Pregnancy Complications
4. Discussion
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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HLA-G Allele | n | sHLA-G (U/mL) | ||||
---|---|---|---|---|---|---|
Me | Min | Max | Q25 | Q75 | ||
105N | 3 | 6.10 | 3.80 | 16.30 | 3.80 | 16.30 |
106 | 5 | 6.60 | 1.00 | 10.80 | 2.00 | 7.80 |
10101 | 65 | 15.40 | 1.00 | 257.40 | 9.70 | 35.70 |
10102 | 42 | 10.75 | 2.00 | 269.60 | 7.00 | 25.20 |
10103 | 8 | 11.00 | 2.00 | 29.90 | 5.55 | 16.35 |
10106 | 6 | 10.90 | 2.70 | 41.50 | 4.20 | 14.00 |
10108 | 5 | 12.20 | 2.20 | 36.10 | 9.10 | 36.10 |
10110 | 1 | 18.60 | 18.60 | 18.60 | 18.60 | 18.60 |
10401 | 7 | 16.70 | 2.00 | 147.10 | 2.70 | 51.70 |
10402 | 1 | 20.80 | 20.80 | 20.80 | 20.80 | 20.80 |
10403 | 1 | 9.00 | 9.00 | 9.00 | 9.00 | 9.00 |
Total | 144 | 12.30 | 1.00 | 269.60 | 6.80 | 28.95 |
Group | n | sHLA-G (U/mL) | ||||
---|---|---|---|---|---|---|
Me | Min | Max | Q25 | Q75 | ||
APS; n = 57 | 57 | 11.90 | 1.00 | 458.00 | 8.00 | 22.20 |
PE; n = 28 | 28 | 10.10 | 1.70 | 100.20 | 5.25 | 14.55 |
IUGR; n = 18 | 18 | 14.90 | 2.40 | 160.00 | 4.60 | 37.70 |
C; n = 72 | 72 | 12.30 | 1.00 | 269.60 | 6.80 | 28.95 |
Total | 175 | 11.40 | 1.00 | 458.00 | 6.60 | 23.40 |
The −725 C>G Polymorphism | ||||||||||
Polymorphism in Women | APS n = 70 | PE n = 48 | IUGR n = 34 | RSA n = 58 | C n = 89 | |||||
n | % | n | % | n | % | n | % | n | % | |
C/G | 21 | 30.00 | 14 | 29.17 | 10 | 29.41 | 14 | 20.69 | 19 | 21.35 |
C/C | 47 | 67.14 | 34 | 70.83 | 24 | 70.59 | 46 | 79.31 | 69 | 77.53 |
G/G | 2 | 2.86 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 1 | 1.12 |
Polymorphism in Men | APS n = 54 | PE n = 43 | IUGR n = 35 | RSA n = 58 | C n = 86 | |||||
n | % | n | % | n | % | n | % | n | % | |
C/G | 15 | 27.78 | 14 | 32.56 | 13 | 37.14 | 12 | 20.69 | 22 | 25.58 |
C/C | 38 | 70.37 | 28 | 65.12 | 22 | 62.86 | 45 | 77.59 | 63 | 73.26 |
G/G | 1 | 1.85 | 1 | 2.33 | 0 | 0.00 | 1 | 1.72 | 1 | 1.16 |
Allele | Allele Shared by Both Partners | APS n = 53 | PE n = 39 | IUGR n = 32 | RSA n = 58 | C n = 80 | |||||
---|---|---|---|---|---|---|---|---|---|---|---|
n | % | n | % | n | % | n | % | n | % | ||
the HLA-G −725 C>G polymorphism | none | 1 | 1.89 | 1 | 2.56 | 0 | 0.00 | 36 | 62.07 | 1 | 1.25 |
one partner | 21 | 39.62 | 11 | 28.21 | 14 | 43.75 | 18 | 31.03 | 28 | 35.00 | |
both partners | 31 | 58.49 | 27 | 69.23 | 18 | 56.25 | 4 | 6.90 | 51 | 63.75 |
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Sipak, O.; Rył, A.; Grzywacz, A.; Laszczyńska, M.; Zimny, M.; Karakiewicz, B.; Rotter, I.; Kosik-Bogacka, D.; Cybulski, C. The Relationship between the HLA-G Polymorphism and sHLA-G Levels in Parental Pairs with High-Risk Pregnancy. Int. J. Environ. Res. Public Health 2019, 16, 1546. https://doi.org/10.3390/ijerph16091546
Sipak O, Rył A, Grzywacz A, Laszczyńska M, Zimny M, Karakiewicz B, Rotter I, Kosik-Bogacka D, Cybulski C. The Relationship between the HLA-G Polymorphism and sHLA-G Levels in Parental Pairs with High-Risk Pregnancy. International Journal of Environmental Research and Public Health. 2019; 16(9):1546. https://doi.org/10.3390/ijerph16091546
Chicago/Turabian StyleSipak, Olimpia, Aleksandra Rył, Anna Grzywacz, Maria Laszczyńska, Małgorzata Zimny, Beata Karakiewicz, Iwona Rotter, Danuta Kosik-Bogacka, and Cezary Cybulski. 2019. "The Relationship between the HLA-G Polymorphism and sHLA-G Levels in Parental Pairs with High-Risk Pregnancy" International Journal of Environmental Research and Public Health 16, no. 9: 1546. https://doi.org/10.3390/ijerph16091546
APA StyleSipak, O., Rył, A., Grzywacz, A., Laszczyńska, M., Zimny, M., Karakiewicz, B., Rotter, I., Kosik-Bogacka, D., & Cybulski, C. (2019). The Relationship between the HLA-G Polymorphism and sHLA-G Levels in Parental Pairs with High-Risk Pregnancy. International Journal of Environmental Research and Public Health, 16(9), 1546. https://doi.org/10.3390/ijerph16091546