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

Author

Ying Wang, Keke Wang, Tianbi Han, Ping Zhang, Xi Chen, Weiwei Wu, Yongliang Feng, Hailan Yang, Mei Li, Bingjie Xie, Pengge Guo, Joshua L. Warren, Xiaoming Shi, Suping Wang, and Yawei Zhang

Subjects
Mixture analysis, Multi-metals, Preeclampsia, Pre-pregnancy BMI, Environmental sciences, GE1-350
Abstract

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.

Published
2020
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2. Single Nucleotide Polymorphisms in CDKAL1 Gene Are Associated with Risk of Gestational Diabetes Mellitus in Chinese Population

Author

Keke Wang, Qiong Chen, Yongliang Feng, Hailan Yang, Weiwei Wu, Ping Zhang, Ying Wang, Jamie Ko, Feng Zhao, Wenqiong Du, Feifei Yang, Tianbi Han, Suping Wang, and Yawei Zhang

Subjects
Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Gestational diabetes mellitus (GDM) is a growing public health concern for many reasons, and its etiology remains unclear. Due to the similarity of its pathophysiology with type 2 diabetes (T2DM), we evaluated the relationship between published T2DM susceptibility genes and the risk of GDM. A total of 303 SNPs from genes including IRS1, IGF2BP2, CDKAL1, GCK, TCF7L2, KCNQ1, and KCNJ11 and the risk of GDM were examined in a nested case-control study with 321 GDM cases and 316 controls. The odds ratios (ORs) and their 95% confidence interval (95% CI) were estimated by unconditional logistical regression as a measure of the associations between genotypes and GDM in additive, recessive, dominant, and codominant models adjusting for maternal age, maternal BMI, parity, and family history of diabetes. At the gene level, CDKAL1 was associated with GDM risk. SNPs in the CDKAL1 gene including rs4712527, rs7748720, rs9350276, and rs6938256 were associated with reduced GDM risk. However, SNPs including rs9295478, rs6935599, and rs7747752 were associated with elevated GDM risk. After adjusting for multiple comparisons, rs9295478 and rs6935599 were still significant across the additive, recessive, and codominant models; rs7748720 and rs6938256 were significant in dominant and codominant models; and rs4712527 was only significant in the codominant model. Our study provides evidence for an association between the CDKAL1 gene and risk of GDM. However, its role in the GDM pathogenesis still needs to be verified by further studies.

Published
2019
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3. Association of CPT1A gene polymorphism with the risk of gestational diabetes mellitus: a case-control study

Author

Weiwei Wu, Mengzhu Guo, Yongliang Feng, Feng Zhao, Wenqiong Du, Yawei Zhang, Suping Wang, Qingwen Ren, Tianbi Han, Wangjun Li, Feifei Yang, and Jinbo Li

Subjects
0301 basic medicine, Adult, Candidate gene, endocrine system diseases, Single-nucleotide polymorphism, Type 2 diabetes, Bioinformatics, Polymorphism, Single Nucleotide, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Pregnancy, Diabetes mellitus, medicine, Genetics, Humans, Genetic Predisposition to Disease, Genetics (clinical), 030219 obstetrics & reproductive medicine, Carnitine O-Palmitoyltransferase, business.industry, Case-control study, Obstetrics and Gynecology, nutritional and metabolic diseases, General Medicine, medicine.disease, female genital diseases and pregnancy complications, Gestational diabetes, Diabetes, Gestational, 030104 developmental biology, Reproductive Medicine, Haplotypes, Case-Control Studies, Female, business, Body mass index, Developmental Biology
Abstract

PURPOSE: Gestational diabetes mellitus (GDM) is a growing public health problem worldwide and its etiology remains unclear. The pathophysiology of GDM is similar to that of type 2 diabetes (T2DM) and insulin resistance (IR) is the main reason for the development of GDM. Carnitine palmitoyltransferase 1A (CPT1A) is a candidate gene for metabolic disorders; however, the association of the CPT1A gene and GDM has not yet been studied. We aimed to explore whether single-nucleotide polymorphisms (SNPs) of the CPT1A gene could influence the risk of GDM. METHODS: We examined 18 single-nucleotide polymorphisms (SNPs) in the CPT1A gene and the risk of GDM in a nested case-control study of 334 GDM patients and 334 controls. The controls who had no GDM were randomly selected through matching to cases by age and residence. RESULTS: After adjusting the family history of diabetes, pre-pregnancy body mass index, and multiple comparison correction, the CPT1A rs2846194 and rs2602814 were associated with reduced GDM risk while rs59506005 was associated with elevated GDM risk. Moreover, the GGAC haplotype in the CPT1A gene (rs17399246 rs1016873 rs11228450 rs10896396) was associated with a reduced risk of GDM. CONCLUSION: Our study provides evidence for an association between genetic polymorphisms in the CPT1A and the risk of GDM.

Published
2020

4. Association between AMPKα1 gene polymorphisms and gestational diabetes in the Chinese population: A case-control study

Author

Weiwei Wu, Jinbo Li, Feng Zhao, Feifei Yang, Tianbi Han, Suping Wang, Yongliang Feng, Wangjun Li, Mengzhu Guo, Wenqiong Du, Yawei Zhang, and Qingwen Ren

Subjects
Adult, medicine.medical_specialty, China, Genotype, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Single-nucleotide polymorphism, AMP-Activated Protein Kinases, Polymorphism, Single Nucleotide, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Gene Frequency, Pregnancy, Risk Factors, Diabetes mellitus, Internal Medicine, medicine, Humans, Genetic Predisposition to Disease, 030212 general & internal medicine, Alleles, Retrospective Studies, Obstetrics, business.industry, Incidence, Haplotype, Case-control study, Odds ratio, medicine.disease, Chinese people, Gestational diabetes, Diabetes, Gestational, Haplotypes, RNA, Female, business, Body mass index, Follow-Up Studies
Abstract

AIM The aim is to examine the association between seven candidate single nucleotide polymorphisms in AMPKα1 and gestational diabetes in Chinese people. METHOD We used a matched nested case-control study design, individuals including 334 participants with gestational diabetes and 334 healthy pregnant women. Confirmed 334 gestational diabetes cases and maternal age and district of residence matched controls (1:1) were enrolled. We examined seven candidate single nucleotide polymorphisms in AMPKα1 gene and the risk of gestational diabetes. The associations were estimated in Co-dominant, Dominant, Recessive, and Alleles models. The odds ratios (ORs) and their 95% confidence intervals (95% CI) were estimated by unconditional logistical regression as a measure of the associations between genotypes and gestational diabetes adjusting for maternal age, prepregnancy body mass index (BMI), fetal sex and parity. RESULT At the gene level, we found that AMPKα1 was associated with gestational diabetes (p = 0.008). After adjusting the covariates and multiple comparison correction, AMPKα1 (rsc1002424, rs10053664, rs13361707) polymorphisms were associated with the risk of gestational diabetes. In addition, gestational diabetes was related to the AAGGA haplotype comprising rs1002424, rs2570091, rs10053664, rs13361707 and rs3805486 in the haplotype models (p = 0.011). CONCLUSIONS This study provides evidence that the AMPKα1 genotypes (rs1002424 G/A, rs10053664 A/G, rs13361707 A/G) and the haplotype (AAGGA) are relevant genetic factors in a Chinese population with gestational diabetes.

Published
2020

5. Polymorphisms in oxidative stress, metabolic detoxification, and immune function genes, maternal exposure to ambient air pollution, and risk of preterm birth in Taiyuan, China

Author

Qingwen Ren, Mengzhu Guo, Yawei Zhang, Feifei Yang, Suping Wang, Wangjun Li, Tianbi Han, Jinbo Li, Weiwei Wu, Yongliang Feng, and Nan Zhao

Subjects
China, Physiology, Single-nucleotide polymorphism, 010501 environmental sciences, Biology, medicine.disease_cause, 01 natural sciences, Biochemistry, Preeclampsia, 03 medical and health sciences, Immune System Phenomena, 0302 clinical medicine, Immune system, Interquartile range, Pregnancy, Air Pollution, Genotype, medicine, Humans, 030212 general & internal medicine, Air quality index, 0105 earth and related environmental sciences, General Environmental Science, Pollutant, Air Pollutants, Immunity, Infant, Newborn, medicine.disease, Oxidative Stress, Maternal Exposure, Premature Birth, Female, Particulate Matter, Oxidative stress
Abstract

Exposure to air pollutants may be associated with preterm birth (PB) through oxidative stress, metabolic detoxification, and immune system processes. However, no study has investigated the interactive effects of maternal air pollution and genetic polymorphisms in these pathways on risk of PB. The study included 126 PB and 310 term births. A total of 177 single nucleotide polymorphisms (SNPs) in oxidative stress, immune function, and metabolic detoxification-related genes were examined and analyzed. The China air quality index (AQI) was used as an overall estimation of ambient air pollutants. Among 177 SNPs, four SNPs (GPX4-rs376102, GLRX-rs889224, VEGFA-rs3025039, and IL1A-rs3783550) were found to have significant interactions with AQI on the risk of PB (Pinteraction were 0.001, 0.003, 0.03, and 0.04, respectively). After being stratified by the maternal genotypes in these four SNPs, 1.38 to 1.76 times of the risk of PB were observed as per interquartile range increase in maternal AQI among women who carried the GPX4-rs376102 AC/CC genotypes, the GLRX-rs889224 TT genotype, the VEGFA-rs3025039 CC genotype, or the IL1A-rs3783550 GT/TT genotypes. After adjustment for multiple comparisons, only GPX4-rs376102 and AQI interaction remained statistically significant (false discovery rate (FDR)=0.17). After additional stratification by preeclampsia (PE) status, a strongest association was observed in women who carried the GPX4-rs376102 AC/CC genotypes (OR, 2.26; 95% CI, 1.41–3.65, Pinteraction=0.0002, FDR=0.035) in the PE group. Our study provided the first evidence that association between maternal air pollution and PB risk may be modified by the genetic polymorphisms in oxidative stress and immune function genes. Future large studies are necessary to replicate and confirm the observed associations.

Published
2020

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