Table 3.
Results of included studies.
| Sl no: | Author, Year | Gene names/miRNA's | SNPs | Statistical analyses | Effect size; P-value* |
|---|---|---|---|---|---|
| Candidate gene studies | |||||
| 1) | A.S. Kvehaugen(48) | RGS2 | C1114G: rs4606 | Logistic regression, Hosmer-Lemeshow goodness of fit | Later- life hypertension and Early-Onset PE: CG: OR = 7.90, 95% CI (1.30–4.82)a; 0.025 CG + GG: OR = 7.96, 95% CI (1.33–47.8)a; 0.023 Later-life hypertension and PE: GG: OR = 1.46, 95% CI (1.02- 2.09)b; 0.037 Stage 2 hypertension and PE: GG: OR = 1.93, 95% CI (1.05- 3.53); 0.033 CG + GG: OR = 1.43, 95% CI (1.02- 2.00); 0.036 |
| 2) | I. Romagnuolo (44) | LPA | + 93C > T: rs1853021, +121G > A: rs1800769 |
Chi-square test, Kruskall-Wallis test, linear regression | As allelic burden Lipoprotein(a) concentrations P = 0.001 Influence of allelic burden on PE and still birth risk P = 0.06 |
| 3) | I.V. da Silva (45) | AQP3 | rs2231231 | Fisher exact test, Chi-Square, binary logistic regression, dominant and recessive models | Later-life hypertension: AA + AC: OR = 3.53, 95% CI (1.24–10.04)c; 0.018 AA: OR = 7.22, 95% CI (1.59–32.82)c; 0.011 AQP3 (rs2231231) correlated with CVD risk in women with prior PE AA + AC: Genotype distributions different in the 4 groups of womend; P = 0.026 |
| MicroRNA studies | |||||
| 4) | N. Dayan (47) | miR-122-5p, miR-126-3p, miR-146a-5p |
_ | Multivariate linear and logistic regression, Spearman correlation coefficients | History of PE in ACS patients: miR-122-5p: OR = .66, 95% CI (0.47–0.92)e,f; 0.009 |
| miR-126-3p: OR = 0.48, 95% CI (0.29–0.78)e,f; 0.002 | |||||
| miR-146a-5p: OR = 0.57, 95% CI (0.35–0.91)e,f; 0.017 | |||||
| 5) | K. Schlosser (46) | miR-206 | _ | D’Agostino Pearson test, Mann-Whitney or unpaired t-test, Fishers Exact test, P-values and Benjamini-Hochberg false discovery rate (FDR) values calculated using EdgeR statistical software package | miR-206 altered in all 4 cohorts. ACS Cohort 1: (prior PE Vs normotensive) Fold change = -10.6; FDR adjusted P-value** = 6.98E-04 Non-ACS Cohort 2: (prior PE Vs normotensive) Fold change = -1.8; FDR adjusted P-value** = 6.21E-01 Cohort 3: (ACS Vs Non-ACS) Fold change = 6.9; FDR adjusted P-value** = 8.65E-09 Cohort 4: (Current PE Vs normotensive: published literature) Fold change = 1.4, miR-206: upregulated in PE |
| Most significant altered enrichment pathway common to PE and ACS: Wnt signaling Most interacted genes with miR-206 in the gene target interaction network: NFAT5, CCND2, SMAD2 | |||||
| Epigenetic study | |||||
| 6) | C. Oudejans (43) | Genes associated with 12 differentially methylated regions with potential CVD risk following PE: AK056657, HIVEP3, PCDHA1, STAG2, NPIPL1, SRPK3, PSMD4, C4orf48, AB020652, DHX58, IGHE |
_ | Statistical testing for Differential DNA methylation, statistical correction for multiple hypothesis testing and ranking conducted using SeqMonk tool, Statistical filter > Chi-square > fwd/rev |
Effect size not mentioned |
ACS, acute coronary syndrome; 95% CI, 95% confidence interval; CVD, cardiovascular disease; miRNAs, micro RNAs; OR, odds ratio; PE, preeclampsia; SNPs, single nucleotide polymorphisms.
a
Adjusted for age and BMI.
b
Adjusted for history of PE.
c
Adjusted for age.
d
Group 1: PE and hypertensive women, Group 2: PE and normal blood pressure post-pregnancy, Group 3: normal blood pressure during pregnancy and hypertensive women, Group 4: normal blood pressure during and post-pregnancy.
e
Adjusted for chronic hypertension.
f
miRNAs inversely associated with history of PE;
*
P significance <0.05.
**
FDR-adjusted P-value <0.05.