
Figure 1.
PRISMA

Figure 2.
Forest plot for the association of IL1A (rs17561) gene polymorphism with PE risk (a) allelic, (b) recessive, (c) dominant, and (d) over-dominant model.

Figure 3.
Forest plot for the association of IFN-γ (rs2430561) gene polymorphism with PE risk (a) allelic, (b) recessive, (c) dominant, and (d) over-dominant model.

Figure 4.
Forest plot for the association of STOX1 (rs1341667) gene polymorphism with PE risk (a) allelic, (b) recessive, (c) dominant, and (d) over-dominant model.

Figure 5.
Forest plot for the association of PPAR-γ (rs1801282) gene polymorphism with PE risk (a) allelic, (b) recessive, (c) dominant, and (d) over-dominant model.

Figure 6.
Sensitivity analysis for IL1A (rs17561) among PE cases and controls in all genetic models.

Figure 7.
Sensitivity analysis for IFN-γ (rs2430561) among PE cases and controls in all genetic models.

Figure 8.
Sensitivity analysis for STOX1 (rs1341667) among PE cases and controls in all genetic models.

Figure 9.
Sensitivity analysis for PPAR-γ (rs1801282) among PE cases and controls in all genetic models.

Figure 10.
The Protein-Protein Interaction (PPI) network of differentially expressed genes (DEGs) among the selected genes associated with PE. We present the total clusters of the PPI network, featuring 8 nodes and 7 edges.

Figure 11.
Circos plot visually represents the chromosomal relationships among the selected SNPs, focusing on IL1A (rs17561).
Table 1.
Characteristics of the studies for the association of IL1A rs17561, IFN-γ rs2430561, STOX1 rs1341667, and PPAR-γ rs1801282 gene polymorphism with PE
| Gene | Study | Ethnicity | Country | PE Cases | Controls | HWE P-value | HWE adjusted P-value | NOS Score | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| AC_Cases | CC_Cases | AA_Cases | AC_Controls | CC_Controls | AA_Controls | |||||||
| IL1A rs (17561) | Li et al., 2014[5] | Asian | China | 53 | 344 | 5 | 111 | 436 | 7 | 0 | 0 | 8 |
| Andraweera et al., 2016[10] | Asian | Sri Lanka | 77 | 79 | 16 | 92 | 60 | 16 | 0.1865 | 0.1865 | 7 | |
| Wu et al., 2017[11] | Asian | China | 15 | 76 | 0 | 39 | 192 | 1 | 0 | 0 | 7 | |
| TT_Cases | TA_Cases | AA_Cases | TT_Controls | TA_Controls | AA_Controls | |||||||
| IFN-γ (rs2430561) | Kamali-Sarvestani et al., 2006[12] | Asian | Iran | 21 | 66 | 42 | 30 | 78 | 53 | 0.8903 | 0.8903 | 6 |
| Daher et al., 2006[13] | Brazil | 6 | 25 | 24 | 22 | 38 | 29 | 0.1842 | 0.8776 | 7 | ||
| Daher et al., 2006[13] | Brazil | 9 | 52 | 34 | 17 | 43 | 36 | 0.5075 | 0.8776 | 8 | ||
| De Lima et al., 2009[14] | Caucasian | Brazil | 7 | 46 | 32 | 18 | 45 | 33 | 0.7021 | 0.8776 | 8 | |
| Pinheiro et al., 2015[15] | Caucasian | Brazil | 33 | 51 | 32 | 5 | 40 | 62 | 0.6497 | 0.8776 | 7 | |
| TT_Cases | TC_Cases | CC_Cases | TT_Controls | TC_Controls | CC_Controls | |||||||
| STOX1 (rs1341667) | Kim et al., 2009[18] | Asian | Korea | 155 | 42 | 5 | 150 | 53 | 1 | 0.1041 | 0.4164 | 7 |
| Fenstad et al., 2010[19] | Caucasian | Norway | 124 | 450 | 412 | 245 | 931 | 840 | 0.5981 | 0.9707 | 7 | |
| Pinarbasi et al., 2020[20] | Asian | Turkey | 108 | 280 | 112 | 143 | 249 | 108 | 0.9839 | 0.9839 | 7 | |
| Bildirici et al., 2023[17] | Asian | Turkey | 10 | 31 | 9 | 18 | 23 | 9 | 0.728 | 0.9707 | 8 | |
| CC_Cases | CG_Cases | GG_Cases | CC_Controls | CG_Controls | GG_Controls | |||||||
| PPAR-γ (rs1801282) | Laasanen et al., 2002[16] | Caucasian | Finland | 95 | 36 | 2 | 76 | 34 | 5 | 0.6334 | 0.6334 | 8 |
| Ghorbani et al., 2021[21] | Asian | Iran | 75 | 25 | 0 | 77 | 23 | 0 | 0.1938 | 0.5814 | 6 | |
| Liu et al., 2021[9] | Caucasian | France | 26 | 8 | 1 | 1297 | 301 | 15 | 0.5922 | 0.6334 | 8 | |
Table 3.
Subgroup analysis for the association of STOX1 rs1341667 gene polymorphism with PE.
| Model | Ethnicity | Number of studies | OR | Test of association 95% CI | p-value | Model | Test of heterogeneity p-value | I2 |
|---|---|---|---|---|---|---|---|---|
| Allele contrast (A vs. a) | Overall | 4 | 0.9573 | [0.8739; 1.0486] | 0.347607 | Fixed | 0.3168 | 0.1503 |
| Asian | 3 | 0.8704 | [0.7456; 1.0162] | 0.079072 | Fixed | 0.5181 | 0 | |
| Caucasian | 1 | 1.0067 | [0.8994; 1.1268] | 0.907561 | Fixed | NA | NA | |
| Recessive model (AA vs. Aa+aa) | Overall | 4 | 0.8644 | [0.6250; 1.1955] | 0.378488 | Random | 0.0343 | 0.6532 |
| Asian | 3 | 0.7751 | [0.4843; 1.2405] | 0.288338 | Random | 0.0621 | 0.6401 | |
| Caucasian | 1 | 1.0398 | [0.8255; 1.3098] | 0.740104 | Fixed | NA | NA | |
| Dominant model (AA+Aa vs. aa) | Overall | 4 | 0.9803 | [0.8559; 1.1229] | 0.774395 | Fixed | 0.5249 | 0 |
| Asian | 3 | 0.9317 | [0.7009; 1.2385] | 0.626105 | Fixed | 0.354 | 0.0371 | |
| Caucasian | 1 | 0.9951 | [0.8527; 1.1614] | 0.950762 | Fixed | NA | NA | |
| Overdominant (Aa vs. AA+aa) | Overall | 4 | 1.0762 | [0.8331; 1.3902] | 0.574082 | Random | 0.0561 | 0.603 |
| Asian | 3 | 1.1554 | [0.7391; 1.8061] | 0.526314 | Random | 0.0609 | 0.6426 | |
| Caucasian | 1 | 0.9784 | [0.8397; 1.1400] | 0.779761 | Fixed | NA | NA | |
| pairwise 1 (AA vs. aa) | Overall | 4 | 0.9008 | [0.7371; 1.0998] | 0.303905 | Fixed | 0.1801 | 0.3863 |
| Asian | 3 | 0.69 | [0.4893; 0.9731] | 0.034376 | Fixed | 0.4948 | 0 | |
| Caucasian | 1 | 1.0319 | [0.8068; 1.3198] | 0.802505 | Fixed | NA | NA | |
| pairwise 2 (AA vs. Aa) | Overall | 4 | 0.8681 | [0.6008; 1.2544] | 0.451454 | Random | 0.0171 | 0.7051 |
| Asian | 3 | 0.7741 | [0.4391; 1.3646] | 0.376068 | Random | 0.0244 | 0.7308 | |
| Caucasian | 1 | 1.0471 | [0.8208; 1.3359] | 0.711047 | Fixed | NA | NA | |
| pairwise 3 (Aa vs. aa) | Overall | 4 | 1.0029 | [0.8692; 1.1572] | 0.968297 | Fixed | 0.3458 | 0.0946 |
| Asian | 3 | 1.0639 | [0.7889; 1.4347] | 0.684766 | Fixed | 0.2102 | 0.3588 | |
| Caucasian | 1 | 0.9855 | [0.8373; 1.1599] | 0.860306 | Fixed | NA | NA |
Table 4.
Subgroup analysis for association of PPAR-γ rs1801282 gene polymorphism with PE.
| Model | Ethnicity | Number of studies | OR | Test of association 95% Cl | p-value | Model | Test of heterogeneity p-value | I2 |
|---|---|---|---|---|---|---|---|---|
| Allele contrast (A vs. a) | Overall | 3 | 1.0252 | [0.7404; 1.4197] | 0.880652 | Fixed | 0.2569 | 0.2642 |
| Asian | 1 | 0.9096 | [0.4974; 1.6634] | 0.758349 | Fixed | NA | NA | |
| Caucasian | 2 | 1.0768 | [0.7316; 1.5849] | 0.707445 | Fixed | 0.1135 | 0.6008 | |
| Recessive model (AA vs. Aa+aa) | Overall | 3 | 1.0002 | [0.6944; 1.4408] | 0.999026 | Fixed | 0.4203 | 0 |
| Asian | 1 | 0.8961 | [0.4681; 1.7156] | 0.740601 | Fixed | NA | NA | |
| Caucasian | 2 | 1.0523 | [0.6769; 1.6358] | 0.820909 | Fixed | 0.2098 | 0.3641 | |
| Dominant model (AA+Aa vs. aa) | Overall | 2 | 1.0613 | [0.1197; 9.4081] | 0.957354 | Random | 0.0973 | 0.6364 |
| Asian | 0 | NA | Fixed | NA | NA | |||
| Caucasian | 2 | 1.0613 | [0.1197; 9.4081] | 0.957354 | Random | 0.0973 | 0.6364 | |
| Overdominant (Aa vs. AA + aa) | Overall | 3 | 1.0367 | [0.7141; 1.5050] | 0.849601 | Fixed | 0.7199 | 0 |
| Asian | 1 | 1.1159 | [0.5829; 2.1365] | 0.740601 | Fixed | NA | NA | |
| Caucasian | 2 | 0.9999 | [0.6343; 1.5762] | 0.999641 | Fixed | 0.4449 | 0 | |
| pairwl (AA vs. aa) | Overall | 2 | 1.0518 | [0.1067; 10.3726] | 0.965492 | Random | 0.0835 | 0.6662 |
| Asian | 0 | NA | Fixed | NA | NA | |||
| Caucasian | 2 | 1.0518 | [0.1067; 10.3726] | 0.965492 | Random | 0.0835 | 0.6662 | |
| pairw2 (AA vs. Aa) | Overall | 3 | 0.9773 | [0.6723; 1.4208] | 0.904274 | Fixed | 0.6343 | 0 |
| Asian | 1 | 0.8961 | [0.4681; 1.7156] | 0.740601 | Fixed | NA | NA | |
| Caucasian | 2 | 1.0203 | [0.6456; 1.6127] | 0.931304 | Fixed | 0.3687 | 0 | |
| pairw3 (Aa vs. aa) | Overall | 2 | 1.2702 | [0.3345; 4.8237] | 0.725342 | Fixed | 0.1755 | 0.4553 |
| Asian | 0 | NA | Fixed | NA | NA | |||
| Caucasian | 2 | 1.2702 | [0.3345; 4.8237] | 0.725342 | Fixed | 0.1755 | 0.4553 |
Table 5.
Emphasizing the importance of determining an appropriate sample size is crucial for accurately evaluating statistical significance and ensuring the reliability of findings in genetic association studies, especially when investigating specific polymorphisms. The estimation of sample size plays a pivotal role in determining the statistical power of these studies
| Gene | SNP | No. of Studies | Cases | Control | α err prob | Power (1-β err prob) |
|---|---|---|---|---|---|---|
| IL1A | rs17561 | 3 | 665 | 954 | 0.02303 | 0.9 |
| IFN-γ | rs2430561 | 5 | 480 | 549 | 0.05343 | 0.9 |
| STOX1 | rs1341667 | 4 | 1738 | 2770 | 0.000495 | 0.9 |
| PPAR-γ | rs1801282 | 3 | 268 | 1828 | 0.06146 | 0.9 |
