Polymorphisms in Sex Hormone Metabolism Genes and Risk of Preeclampsia in Taiyuan, China.

OBJECTIVE: Aberrant synthesis and metabolism of sex hormone are likely to be associated with alterations in vascular function in preeclampsia (PE). The study aims to investigate whether single nucleotide polymorphisms (SNPs) in sex hormone-related genes are associated with PE. METHOD: We performed a nested case-control study including 436 pregnant women (203 PE and 233 healthy or normal pregnant women) to investigate associations between 96 SNPs in 28 sex hormone-related genes and risk of PE. RESULTS: TXNRD2/COMT rs3788314 and SULT1A2/SULT1A1 rs4788073 were associated with an increased risk of PE overall (ptrend = 0.004 and 0.003, respectively), early-onset PE (ptrend = 0.007 and 0.009, respectively), and severe PE (ptrend = 0.002 and 0.005, respectively). Additionally, CYP17A1 rs4919690 and rs4919687 and LHCGR rs10180731 were associated with an increased risk of severe PE (ptrend = 0.005, 0.006, and 0.014, respectively), while GNRHR rs2630488 was associated with a decreased risk of severe PE (ptrend = 0.014). We also observed that HSD17B3 rs8190512 was associated with a decreased risk of early-onset PE (ptrend = 0.003). We observed strong linkage disequilibrium in SULF1 (rs10106958, rs7813987, and rs6990375). CONCLUSIONS: Our study suggested that genetic polymorphisms in TXNRD2/COMT, SULT1A2/SULT1A1, CYP17A1, HSD17B3, GNRHR, LHCGR, and SULF1 might play a role in PE, especially in early-onset PE and severe PE. Future studies are warranted to replicate the observed associations and their functional mechanisms.

Polymorphisms in complement genes and risk of preeclampsia in Taiyuan, China.

BACKGROUND AND OBJECTIVES: Altered immune response may be a part of the pathogenesis of preeclampsia. The few epidemiologic studies that have investigated the associations between genetic variations in the complement system genes and preeclampsia risk have reached inconsistent results. The aim of this study is to determine if polymorphisms in the complement system genes could influence the risk of preeclampsia. METHODS: We examined 51 SNPs in the C3, C5, C6, MASP1, MBL2 and CD55 genes and the risk of preeclampsia and its clinical subtypes in a nested case-control study of 203 preeclampsia cases and 233 controls. RESULTS: Both C6 and MASP1 were associated with the risk of preeclampsia. C6 (rs7444800, rs4957381) and MASP1 (rs1108450, rs3774282, rs698106) polymorphisms were associated with the risk of early-onset preeclampsia and severe preeclampsia, while MASP1 (rs1357134, rs698090) polymorphisms were associated with the risk of late-onset preeclampsia and severe preeclampsia. CONCLUSIONS: Our study provided novel evidence that genetic variations in complement genes C6 and MASP1were associated with preeclampsia risk, and that the risk varied by preeclampsia subtypes.

Exposure to multiple metals and prevalence for preeclampsia in Taiyuan, China.

BACKGROUND: Several studies with small sample size have reported inconsistent associations between single metal and preeclampsia (PE). Very few studies have investigated metal mixtures and PE. METHODS: Blood concentrations of chromium (Cr), cadmium, mercury (Hg), arsenic (As), lead (Pb), nickel, cobalt, and antimony were measured using inductively coupled plasma-mass spectrometry among 427 PE women and 427 matched controls from Taiyuan, China. Multivariate logistic regression models, weighted quantile sum (WQS) regression, and principal component analysis were employed to examine exposure to single metals and metal mixtures in relation to PE. RESULTS: An increased prevalence of PE was associated with Cr (OR = 1.76, 95% CI: 1.18, 2.62 and 1.90, 1.22, 2.93 for the middle and high vs. low), Hg (OR = 1.60, 95% CI: 1.08, 2.38 for the high vs. low) and As (OR = 1.64, 95% CI: 1.07, 2.52 for the middle vs. low). The WQS index, predominated by Cr, Hg, Pb, and As, was positively associated with PE. A principal component characterized by Cr and As also exhibited excessive association with PE. The highest PE prevalence was found among women who were overweight/obese before pregnancy and had high Cr levels compared to women who had pre-pregnancy normal body mass index (BMI) and low Cr levels. CONCLUSIONS: Our study provided evidence that exposure to multiple metals was associated with increased prevalence of PE, and the observed association with multiple metals was dominated by Cr, As. Our study also suggested that pre-pregnancy BMI might modify the association between Cr and PE.

Zinc Levels and Birth Weight in Pregnant Women with Gestational Diabetes Mellitus: A Matched Cohort Study in China.

BACKGROUND: Zinc (Zn) has been suggested to impact fetal growth. However, the effect may be complicated by gestational diabetes mellitus (GDM) due to its impact on fetal growth and placental transport. This study aims to investigate whether GDM modifies the association between Zn levels and birth weight. METHOD: A cohort matched by GDM was established in Taiyuan, China, between 2012 and 2016, including 752 women with GDM and 744 women without. Dietary Zn intake was assessed during pregnancy. Maternal blood (MB) and cord blood (CB) Zn levels were measured at birth. Birth weight was standardized as the z score and categorized as high (HBW, >4000 g) and low (LBW, <2500 g) groups. Multivariate linear regression and multinomial logistic regression were used to examine the association between Zn levels and birth weight in offspring born to women with or without GDM. RESULTS: 88.8% (N = 1328) of the population had inadequate Zn intake during pregnancy. In women with GDM, MB Zn level was inversely associated with birth weight (ß = -.17; 95% confidence interval (CI), -0.34 to -0.01), while CB Zn level was positively associated with birth weight (ß = .38; 95% CI, 0.06-0.70); suggestive associations were observed between MB Zn level and LBW (odds ratio 2.01; 95% CI, 0.95-4.24) and between CB Zn level and HBW (odds ratio 2.37; 95% CI, 1.08-5.21). CONCLUSIONS: GDM may modify the associations between MB and CB Zn levels and birth weight in this population characterized by insufficient Zn intake. These findings suggest a previously unidentified path of adverse effects of GDM.

Multiple metal concentrations and gestational diabetes mellitus in Taiyuan, China.

BACKGROUND: The association between multiple metal concentrations and gestational diabetes mellitus (GDM) is poorly understood. METHODS: A total of 776 women with GDM and an equal number of controls were included in the study. Concentrations of metals in participants' blood (nickel (Ni), arsenic (As), cadmium (Cd), antimony (Sb), thallium (Tl), mercury (Hg), lead (Pb)) were measured using inductively coupled plasma-mass. We used unconditional logistical regression models to estimate the associations between metals and GDM. We also employed weighted quantile sum (WQS) regression and principal components analysis (PCA) to examine metal mixtures in relation to GDM. RESULTS: An increased risk of GDM was associated with As (OR = 1.49, 95% CI: 1.11, 2.01 for the 2nd tertile vs. the 1st tertile) and Hg (OR = 1.43, 95% CI: 1.09, 1.88 for the 3rd tertile vs. the 1st tertile). In WQS analysis, the WQS index was significantly associated with GDM (OR = 1.20, 95% CI: 1.02, 1.41). The major contributor to the metal mixture index was Hg (69.2%), followed by Pb (12.8%), and As (11.3%). Based on PCA, the second principal component, which was characterized by Hg, Ni, and Pb, was associated with an increased risk of GDM (OR = 1.46, 95% CI: 1.02, 2.08 for the highest quartile vs. the lowest quartile). CONCLUSIONS: Our study results suggest that high metal levels are associated with an increased risk of GDM, and this increased risk is mainly driven by Hg and, to a lesser extent, by Ni, Pb, and As.

SOS1 gene polymorphisms are associated with gestational diabetes mellitus in a Chinese population: Results from a nested case-control study in Taiyuan, China.

Gestational diabetes mellitus is a growing public health concern due to its large disease burden; however, the underlying pathophysiology remains unclear. Therefore, we examined the relationship between 107 single-nucleotide polymorphisms in insulin signalling pathway genes and gestational diabetes mellitus risk using a nested case-control study. The SOS1 rs7598922 GA and AA genotype were statistically significantly associated with reduced gestational diabetes mellitus risk ( ptrend = 0.0006) compared with GG genotype. At the gene level, SOS1 was statistically significantly associated with gestational diabetes mellitus risk after adjusting for multiple comparisons. Moreover, AGGA and GGGG haplotypes in SOS1 gene were associated with reduced risk of gestational diabetes mellitus. Our study provides evidence for an association between the SOS1 gene and risk of gestational diabetes mellitus; however, its role in the pathogenesis of gestational diabetes mellitus will need to be verified by further studies.

Polymorphisms in Inflammatory Mediator Genes and Risk of Preeclampsia in Taiyuan, China.

Excessive maternal inflammatory response is involved in the pathogenesis of preeclampsia. Few epidemiologic studies have investigated the associations between genetic variations in the inflammatory mediator genes and preeclampsia risk, and these studies have reached inconsistent results. We examined 31 single-nucleotide polymorphisms in IL-1A, IL-1B, IL-1R1, IL-2RA, IL-5RA, IL-6, IL-6R, TNFSF11, TNFRSF11A, IL-28RA, IRAK4, and KIT genes and the risk of preeclampsia and its clinical subtypes in a nested case-control study including 203 preeclampsia cases and 233 controls. We found that IL-1R1, IL-5RA, IL-6R, and TNFSF11 were associated with the risk of preeclampsia. Although the significant associations observed for preeclampsia overall were mainly seen for late-onset preeclampsia and severe preeclampsia, IL-6R (rs2229238) and TNFSF11 (rs9525643) polymorphisms were associated with the risk of early-onset preeclampsia. TNFSF11 (rs2200287 and rs2148072) polymorphisms were associated with risk of mild preeclampsia. Our study provided the first evidence that genetic variations in inflammatory mediator genes IL-1R1, IL-6R, TNFSF11, and IL-5RA were associated with preeclampsia risk, and the risk varied by preeclampsia subtypes.

[Ambient PM2.5 during pregnancy and risk on preterm birth].

OBJECTIVE: To investigate the association between ambient fine particulate matter with aerodynamic diameter less than 2.5 µm (PM2.5) and the risk on preterm birth. METHODS: A total of 1 882 pregnant women with local residency of Taiyuan city and underwent delivery at the First Hospital of Shanxi Medical University with the dates of conception between January 1 and December 31, 2013, were enrolled in the study. Information on general demographics, home address and history on pregnancy, lifestyle and related environmental factors were collected through in-person interview. Birth outcomes and maternal complications were abstracted from medical records. Data on the amount of daily average PM2.5 from 8 monitor points in Taiyuan city, between March 1, 2012 and December 31, 2013 were also collected. Individual exposure during pregnancy were calculated using the inverse-distance weighting method, based on home address. Multivariate unconditional logistic regression model was used to examine the associations among PM2.5 exposure, risk of preterm birth and related clinical subtypes. RESULTS: The overall incidence of preterm birth was 8.21% (151/1 839)in 1 839 pregnant women. Exposure to ambient PM2.5 during the second week prior to delivery was associated with an increased risk of preterm birth (OR=1.087, 95% CI: 1.001-1.182 per 10 µg/m(3) increase) and mild preterm birth (OR=1.099, 95% CI: 1.007-1.200 per 10 µg/m(3)). Compared to data from the China Environmental Air Quality Standard, higher level of exposure (≥75 µg/m(3)) of PM2.5 during the second week before delivery was associated with an increased risk of preterm birth (OR=1.008, 95%CI: 1.000-1.017) but the association was mainly seen for mild preterm birth (OR=1.010, 95%CI: 1.001-1.018). CONCLUSIONS: RESULTS from our study showed that exposure to high level of PM2.5 during late pregnancy would increase the risk of preterm birth. Future large studies are needed to examine the association by preterm clinical subtypes and to elucidate potential underlying mechanisms.