Combination of Genetic Markers and Age Effectively Facilitates the Identification of People with High Risk of Preeclampsia in the Han Chinese Population

Abstract

Objective This study aimed to analyze the possible association between known genetic risks and preeclampsia in a Han Chinese population. Methods A total of 156 patients with preeclampsia and 286 healthy Han Chinese women were enrolled and genotyped for 27 genetic alleles associated with preeclampsia in different populations. The association between the genotypes of the individual alleles and preeclampsia and the possible interaction among the alleles were analyzed. Finally logistic models were trained with the genotypes of possible alleles contributing to preeclampsia. Results Seven alleles were significantly or marginally significantly associated with preeclampsia, which involved six genes (rs4762 in AGT, rs1800896 in IL-10, rs1800629 and rs1799724 in TNFα, rs2070744 in NOS3, rs7412 in APOE, and rs2549782 in ERAP2). A multilocus interaction analysis further disclosed an interaction among seven alleles. A logistic model showing individual or synergetic contribution to preeclampsia could reach ~0.67 preeclampsia prediction accuracy in the Han Chinese population, while integration of age information could improve the performance to ~0.75 accuracy using a fivefold training-testing evaluation strategy. Conclusions The genetic factors were closely associated with preeclampsia in the Han Chinese population despite large ethnicity heterogeneity. The genotypes of different alleles also had synergetic interactions.

Polymorphism in maternal HLA-DRB5 is associated with the risk of preeclampsia in Chinese population

“…McGinnis et al performed a GWAS study on PE offspring and identi ed a signi cant susceptibility locus (rs4769613) that was nearby the gene FLT1 encoding FMS like tyrosine kinase 1 [25]. Zhou et al selected multiple genetic risk loci that have been reported to be signi cantly associated with PE in other multiethnic cohorts, performed genotype testing in Chinese PE and healthy pregnancies, and found very few risk alleles or genotypes consistent with previous reports [30,31]. Some risk loci even showed opposite effects, i.e., being protective to the Chinese population for the risk alleles or genotypes reported for other ethnicity, further demonstrating the ethnic speci city of PE genetic susceptibility.…”

“…5A). The model performs as well as those developed previously that are based on both the genotypes of 5 or 8 PE risk loci and clinical factors [31]. We also included the 8 previously identi ed loci and the age and BMI at pregnancy, and trained different regression or machine learning models.…”

“…It is possible that more intersects of risk loci could be identi ed with other cohorts if the power was increased with enlarged cohort size; however, the most signi cantly associated SNPs and genes could still show large heterogeneity. The ethnic heterogeneity of genetic risks in preeclampsia has been reported frequently [27,30,31], though the mechanisms remain unknown.…”

“…The model performance was evaluated based on prediction results of 5-fold cross-validated testing datasets. The parameters for performance assessment, including Speci city (Sp), Sensitivity (Sn), Accuracy (Acc), Precision (Pre), Receiver Operating Characteristic (ROC) curve, the area under ROC curve (AUCroc), Matthews Correlation Coe cient (MCC) and F1-Score, were well de ned in Zhou et al, 2018 31 or elsewhere. The average 5-fold average performance was calculated and assessed.…”

Genetic Variant of Vascular Endothelial Growth Factor (VEGF)-A rs699947 is Associated with Preeclampsia

“…2 Genetic and environmental factors have been known to have contributions for preeclampsia phenotype. [3][4][5] Abnormality of trophoblast invasion to myometrium is followed by endothelial disfunction local in placenta, then spreads to maternal circulation. This abnormality involved unbalanced proangiogenic and antiangiogenic factors.…”