Risk of Recurrent Pregnancy Loss in the Ukrainian Population Using a Combined Effect of Genetic Variants: A Case-Control Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Sample
2.2. Blood Sample Collection, DNA Extraction and Genotyping Procedures
2.3. Association Analysis
2.4. Genetic Risk Score Calculation
2.5. Receiver Operating Characteristic Analysis
3. Results
3.1. Association Analysis
3.2. Receiver Operator Characteristic Analysis
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Locus Name | SNP rsID | EA/NEA | EAF (1000 G *) | OR (95% CI) | p-Value | Case/Control Sample Size | Outcome | Reference | Genotyping Method | Reference |
---|---|---|---|---|---|---|---|---|---|---|
Blood coagulation | ||||||||||
F2 | rs1799963 | A/G | 0.008 | 2.00 (1.00, 4.00) | <0.03 | 342/123 | RPL | [18] | RFLP | [45] |
F5 | rs6025 $ | T/C | 0.012 | 2.5 (1.80, 3.40) | <10−3 | 342/123 | RPL | [18] | RFLP | [45] |
F7 | rs6046 | G/A | 0.89 | - | - | - | - | - | RFLP | [46] |
GP1A | rs1126643 | T/C | 0.40 | - | - | - | - | - | RFLP | [47] |
Hormonal regulation | ||||||||||
ESR1 | rs2234693 ^ | T/C | 0.58 | 1.10 (0.57, 2.13) | >0.05 | 350/646 | RPL | [48] | RFLP | [49] |
ADRB2 | rs1042714 | G/C | 0.41 | - | - | - | - | - | RFLP | [50] |
Endometrium and placental function | ||||||||||
ENOS | Intron-4 ǂ VNTR ^ | B/A | - | 1.005 (0.74, 1.37) | >0.05 | 410/357 | RPL | [51] | Allele-specific PCR | [52] |
ACE | rs1799752 †,$ | D/I | - | 2.06 (1.46, 2.91) | NA | 740/329 | RPL | [28] | Allele-specific PCR | [53] |
Folate metabolism | ||||||||||
MTHFR | rs1801133 $ | T/C | 0.36 | 1.25 (0.93, 1.67) | 0.14 | 1830/3037 | RPL | [38] | RFLP | [54] |
Inflammatory response | ||||||||||
IL6 | 14718 $ | G/C | - | 1.214 (0.88, 1.67) | 0.24 | 230/188 | RPL | [42] | RFLP | [55] |
IL8 | rs2227306 | C/T | 0.61 | - | - | - | - | - | RFLP | [56] |
IL10 | rs1800896 ^ | G/A | 0.45 | 1.27 (0.95, 1.70) | >0.05 | 635/571 | RPL | [41] | RFLP | [57] |
IL10 | rs1800872 | T/G | 0.76 | 3.01 (1.92, 4.72) | <10−4 | 342/123 | Early PL | [40] | RFLP | [58] |
Locus Name | Chr: Position | Variant ID | EA/NEA | EAF Cases/Controls | N Cases/N Controls | EAE | OR (95% CI) | p-Value |
---|---|---|---|---|---|---|---|---|
F2 | 11:46761055 | rs1799963 | A/G | 0.018/0.011 | 110/46 | 0.49 | 1.64 (0.23, 32.48) | 0.66 |
F5 | 1:169519049 | rs6025 | A/G | 0.018/0.022 | 114/46 | −0.22 | 0.80 (0.15, 5.92) | 0.80 |
F7 | 13:113773159 | rs6046 | G/A | 0.89/0.85 | 75/46 | 0.34 | 1.40 (0.65, 3.04) | 0.38 |
GP1A | 5:52347369 | rs1126643 | C/T | 0.63/0.54 | 81/46 | 0.35 | 1.43 (0.85, 2.44) | 0.18 |
ESR1 | 6:152163335 | rs2234693 | T/C | 0.49/0.55 | 110/106 | −0.18 | 0.84 (0.57, 1.23) | 0.37 |
ADRB2 | 5:148206473 | rs1042714 | C/G | 0.60/0.51 | 81/46 | 0.38 | 1.47 (0.86, 2.56) | 0.16 |
ENOS | 15:35147732-35262040 | Intron-4 ǂ VNTR | B/A | 0.83/0.80 | 102/46 | 0.15 | 1.16 (0.63, 2.08) | 0.63 |
ACE | 17:61565890 | rs1799752 † | D/I | 0.52/0.53 | 100/46 | −0.048 | 0.95 (0.59, 1.54) | 0.85 |
MTHFR | 1:11856378 | rs1801133 | T/C | 0.30/0.24 | 114/46 | 0.33 | 1.40 (0.80, 2.51) | 0.25 |
IL6 | 7:22766840 | 14718 | G/C | 0.59/0.56 | 106/106 | 0.11 | 1.10 (0.77, 1.64) | 0.57 |
IL8 | 4:74607055 | rs2227306 | T/C | 0.40/0.37 | 114/106 | 0.11 | 1.10 (0.76, 1.64) | 0.60 |
IL10 | 1:206946897 | rs1800896 | A/G | 0.59/0.49 | 114/106 | 0.47 | 1.60 (1.07, 2.42) | 0.025 |
GRS | 114/106 | 1.56 (1.21, 2.04) | 8.7 × 10−4 |
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Loizidou, E.M.; Kucherenko, A.; Tatarskyy, P.; Chernushyn, S.; Livshyts, G.; Gulkovskyi, R.; Vorobiova, I.; Antipkin, Y.; Gorodna, O.; Kaakinen, M.A.; et al. Risk of Recurrent Pregnancy Loss in the Ukrainian Population Using a Combined Effect of Genetic Variants: A Case-Control Study. Genes 2021, 12, 64. https://doi.org/10.3390/genes12010064
Loizidou EM, Kucherenko A, Tatarskyy P, Chernushyn S, Livshyts G, Gulkovskyi R, Vorobiova I, Antipkin Y, Gorodna O, Kaakinen MA, et al. Risk of Recurrent Pregnancy Loss in the Ukrainian Population Using a Combined Effect of Genetic Variants: A Case-Control Study. Genes. 2021; 12(1):64. https://doi.org/10.3390/genes12010064
Chicago/Turabian StyleLoizidou, Eleni M., Anastasia Kucherenko, Pavlo Tatarskyy, Sergey Chernushyn, Ganna Livshyts, Roman Gulkovskyi, Iryna Vorobiova, Yurii Antipkin, Oleksandra Gorodna, Marika A. Kaakinen, and et al. 2021. "Risk of Recurrent Pregnancy Loss in the Ukrainian Population Using a Combined Effect of Genetic Variants: A Case-Control Study" Genes 12, no. 1: 64. https://doi.org/10.3390/genes12010064