Genome-wide association study reveals HSF2, GJA1 and TRIM36 as susceptibility genes for preeclampsia: a community-based population study in Tianjin, China.

BACKGROUND: Preeclampsia (PE) mainly occurs in pregnant women and is hereditary. Several genome-wide association studies (GWAS) on Caucasian samples have reported some gene loci that are associated with preeclampsia. However, these studies have not reached consistent conclusions. No previous GWAS has examined preeclampsia in the Chinese Han population. METHOD: This study aimed to identify common genetic variations associated with preeclampsia in the Chinese Han population through two-stage case‒control studies. The discovery cohort included 92 patients with severe preeclampsia and 187 healthy controls. The validation cohort included 52 patients with preeclampsia and 104 controls. A genome-wide association study was performed to identify putative preeclampsia genes in the discovery cohort, with validation in the validation cohort. RESULTS: In the discovery cohort, GWAS demonstrated that 19 single-nucleotide polymorphisms (SNPs) were associated with preeclampsia (P < 10-5). The pathway analysis revealed that these 19 SNP representative genes were mainly enriched in the adenylyl cyclase-inhibiting G-protein coupled receptor signaling pathway. After validation in the validation cohort, rs13176432 and rs13210237 remained closely related to preeclampsia (P<0.05). In the combined data set, the frequency of the G allele in rs13176432 was significantly higher in cases with preeclampsia than in controls (P = 5 × 10-6). The frequency of the A allele in rs13210237 was higher in the preeclampsia group (P = 8 × 10-6). The rs13210237 representative genes include HSF2 and GJA1, while the rs13176432 representative gene is TRIM36. There were no differences in genotype distribution between the early-onset and late-onset preeclampsia groups (P > 0.05). Furthermore, rs13210237 and rs13176432 were related to preeclampsia in the adjusted regression model (P < 0.000). CONCLUSION: In this study of two independent cohorts, we found that rs13210237 and rs13176432 might be novel preeclampsia-susceptible genetic factors in the Han population in China. However, there was no association between the onset of preeclampsia and these genotypes.

Coal-source acid mine drainage reduced the soil multidrug-dominated antibiotic resistome but increased the heavy metal(loid) resistome and energy production-related metabolism.

A recent global scale study found that mining-impacted environments have multi-antibiotic resistance gene (ARG)-dominated resistomes with an abundance similar to urban sewage but much higher than freshwater sediment. These findings raised concern that mining may increase the risk of ARG environmental proliferation. The current study assessed how typical multimetal(loid)-enriched coal-source acid mine drainage (AMD) contamination affects soil resistomes by comparing with background soils unaffected by AMD. Both contaminated and background soils have multidrug-dominated antibiotic resistomes attributed to the acidic environment. AMD-contaminated soils had a lower relative abundance of ARGs (47.45 ± 23.34 ×/Gb) than background soils (85.47 ± 19.71 ×/Gb) but held high-level heavy metal(loid) resistance genes (MRGs, 133.29 ± 29.36 ×/Gb) and transposase- and insertion sequence-dominated mobile genetic elements (MGEs, 188.51 ± 21.81 ×/Gb), which was 56.26 % and 412.12 % higher than background soils, respectively. Procrustes analysis showed that the microbial community and MGEs exerted more influence on driving heavy metal(loid) resistome variation than antibiotic resistome. The microbial community increased energy production-related metabolism to fulfill the increasing energy needs required by acid and heavy metal(loid) resistance. Horizontal gene transfer (HGT) events primarily exchanged energy- and information-related genes to adapt to the harsh AMD environment. These findings provide new insight into the risk of ARG proliferation in mining environments.

ELABELA improves endothelial cell function via the ELA-APJ axis by activating the PI3K/Akt signalling pathway in HUVECs and EA.hy926 cells.

Destruction of endothelial cells (ECs) function is involved in the structural and functional pathophysiological processes of preeclampsia (PE). Vascular endothelial injury may pre-exist for several years in women that develop PE and may pose increased risks for hypertension, coronary artery disease, and type-2 diabetes mellitus. Previous findings showed that Elabela (ELA), the endogenous ligand of the apelin (APJ) receptor expressed mainly on ECs, may play a protective role in early pregnancy and prevent PE. However, the exact functional role and molecular mechanisms of ELA are unclear. Here, we aimed to classify whether and how ELA improves EC function via the ELA-APJ axis. Two human umbilical vein endothelial cell (HUVEC) lines, namely HUVECs and EA.hy926, were treated with ELA, and then their cellular activities were studied by performing CCK-8 tests, scratch-wound analysis, and tube-formation assays. Doses of ELA exceeding 0.01 µmol/L markedly improved the cell viability, migration, and tube formation ability of HUVECs and EA.hy926 cells. Western blot analysis indicated that the above effects caused by ELA were related to upregulation of the APJ receptor and activation of PI3K/Akt signalling. Further verification tests were performed using the PI3K inhibitor wortmannin, and the results illustrated that inhibiting PI3K/Akt signalling blocked the positive effects of ELA on EC function and APJ receptor expression. Taken together, our findings indicate that ELA may alter EC function via the ELA-APJ axis and PI3K/Akt signalling and that ELA shows promise for use in endothelial dysfunction therapy for preventing and treating PE.

Prehypertension during pregnancy and risk of small for gestational age: a systematic review and meta-analysis.

Objective: Emerging evidence shows that high blood pressure (BP) level even below 140/90 mmHg during pregnancy is associated with increased risk for maternal and infant complications. The meta-analysis evaluated the associations between prehypertension (BP 120-139/80-89 mmHg) during pregnancy and the risk of small for gestational age (SGA), as well as the impact of prehypertension on birth weight (BW).Methods: Databases (PubMed, Embase, and Cochrane Library) were searched for cohort studies with data on prehypertension in pregnancy and adverse obstetrical outcomes, including SGA and/or BW. The relative risks (RRs) of SGA and weighted mean differences (WMD) in BW were calculated and reported with 95% confidence intervals (95% CIs). We calculated pooled RRs using fixed- and random-effects models.Results: A total of 143,835 participants from five cohort studies were included. Prehypertension in pregnancy increased the risk of SGA (RR 1.59, 95%CI 1.44 to 1.76, p < .00001) and lowered BW (WMD -13.71, 95% CI -83.28 to 55.87, p = .70) compared with optimal BP (<120/80 mmHg). In subgroup analyses, for prehypertension in late pregnancy, the risk of SGA was significantly higher than for optimal BP (RR 1.60, 95% CI 1.44 to 1.78).Conclusion: BP within the range of 120-139/80-89 mmHg during pregnancy, as previously defined as prehypertension, particularly in late pregnancy, was associated with a 59% increase in the risk of having an SGA birth.