CYP2E1 C-1054T and 96-bp I/D genetic variations and risk of gestational diabetes mellitus in chinese women: a case-control study

Pu, Yifu; Liu, Qingqing; Hu, Kaifeng; Liu, Xinghui; Bai, Huai; Wu, Yujie; Zhou, Mei; Fan, Ping

doi:10.1186/s12884-023-05742-y

Cited by 3 publications

(1 citation statement)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CYP2E1 (cytochrome P450 2E1) is an abundant hepatic enzyme which participates in arachidonic acid metabolism. SNPs in the gene coding for CYP2E1, including C-1054T, are thought to affect lipid metabolism and insulin resistance, and have been was associated with GDM risk ( 27 , 99 ). Concurrently, metabolites of arachidonic acid produced by CYP450 enzymes, known as epoxyeicosatrienoic acids (EETs), are proposed to enhance insulin sensitivity and glucose metabolism.…”

Section: Subsectionsmentioning

confidence: 99%

Multigenerational diabetes mellitus

Thornton,

Shah,

Lillycrop

et al. 2024

Front. Endocrinol.

View full text Add to dashboard Cite

Gestational diabetes (GDM) changes the maternal metabolic and uterine environment, thus increasing the risk of short- and long-term adverse outcomes for both mother and child. Children of mothers who have GDM during their pregnancy are more likely to develop Type 2 Diabetes (T2D), early-onset cardiovascular disease and GDM when they themselves become pregnant, perpetuating a multigenerational increased risk of metabolic disease. The negative effect of GDM is exacerbated by maternal obesity, which induces a greater derangement of fetal adipogenesis and growth. Multiple factors, including genetic, epigenetic and metabolic, which interact with lifestyle factors and the environment, are likely to contribute to the development of GDM. Genetic factors are particularly important, with 30% of women with GDM having at least one parent with T2D. Fetal epigenetic modifications occur in response to maternal GDM, and may mediate both multi- and transgenerational risk. Changes to the maternal metabolome in GDM are primarily related to fatty acid oxidation, inflammation and insulin resistance. These might be effective early biomarkers allowing the identification of women at risk of GDM prior to the development of hyperglycaemia. The impact of the intra-uterine environment on the developing fetus, “developmental programming”, has a multisystem effect, but its influence on adipogenesis is particularly important as it will determine baseline insulin sensitivity, and the response to future metabolic challenges. Identifying the critical window of metabolic development and developing effective interventions are key to our ability to improve population metabolic health.

show abstract

Section: Subsectionsmentioning

confidence: 99%

Multigenerational diabetes mellitus

Thornton,

Shah,

Lillycrop

et al. 2024

Front. Endocrinol.

View full text Add to dashboard Cite

show abstract

Evidence for causal effects of polycystic ovary syndrome on oxidative stress: a two-sample mendelian randomisation study

2023

BMC Med Genomics

View full text Add to dashboard Cite

Background Polycystic ovary syndrome (PCOS) is often accompanied by increased oxidative stress levels; however, it is still unclear whether PCOS itself is causally related to oxidative stress (OS), whether OS can increase the occurrence of PCOS, and which characteristics of PCOS increase OS levels. Therefore, this study explored the causal relationship between PCOS, its characteristics, and OS. Methods Two-sample bidirectional and two-sample Mendelian randomisation studies were performed based on publicly available statistics from genome-wide association studies. PCOS; its characteristics, such as testosterone, low-density lipoprotein, high-density lipoprotein; and 11 major OS markers (superoxide dismutase, glutathione S-transferase, glutathione peroxidase, catalase, uric acid, zinc, tocopherol, ascorbic acid, retinol, albumin, and total bilirubin), were studied. The main analytical method used was inverse variance weighting (IVW). Pleiotropy was evaluated using the Mendelian randomisation-Egger intercept. Q and P values were used to assess heterogeneity. Results There was no causal relationship between PCOS and the OS indices (all P > 0.05). There was a causal relationship between the OS index, ascorbate level, and PCOS (IVW, odds ratio: 2.112, 95% confidence interval: 1.257–3.549, P = 0.005). In addition, there was a causal relationship between testosterone, low-density lipoprotein, high-density lipoprotein, sex hormone-binding globulin, body mass index, triacylglycerol, age at menarche, and most OS indices according to the IVW method. The F statistics showed that there was no weak instrumental variable. A sensitivity analysis was performed using the leave-one-out method. No pleiotropy was observed. The results were robust, and the conclusions were reliable. Conclusions This study showed for the first time that there was no causal relationship between PCOS and OS. However, there was a causal relationship between the OS index, ascorbate level, and PCOS. It revealed that PCOS itself could not increase OS, and the increase in OS in PCOS was related to other potential factors, such as testosterone, low-density lipoprotein, high-density lipoprotein, sex hormone-binding globulin, body mass index, triacylglycerol, and age at menarche.

show abstract

25-Hydroxyvitamin D, Vitamin D Binding Protein and Gestational Diabetes Mellitus: A Two-Sample Mendelian Randomization Study

Qiu,

Ainiwan,

Huang

et al. 2024

Nutrients

View full text Add to dashboard Cite

Background: Numerous studies have examined whether vitamin D is associated with gestational diabetes mellitus (GDM). Nevertheless, it is still challenging to determine the causality, due to a number of shortcomings in observational research and randomized controlled trials. Objective: Mendelian randomization (MR) with two samples was conducted to investigate the potential causative association between 25-hydroxyvitamin D (25(OH)D), vitamin D binding protein (VDBP) and GDM risk. Methods: Publicly accessible summary data from independent cohorts were used for two-sample MR. For 25(OH)D, we obtained data from UK Biobank, IEU and EBI, then performed a meta-analysis to enhance the statistical power (via METAL); for VDBP, data were obtained from the INTERVAL study; for GDM, data were obtained from FinnGen. The inverse variance weighted (IVW) approach was performed as the main analysis, together with several sensitivity analyses, such as MR–Egger, maximum likelihood, weighted median, and weighted mode. Results: The IVW results revealed a weak negative causal connection between 25(OH)D and GDM risk [OR (95% CI) = 0.71 (0.50, 0.99), p = 0.046]. However, the causal association was unstable according to sensitivity analyses, and Cochran’s Q test revealed significant heterogeneity. After removing BMI-related IVs, the causal association between 25(OH)D and GDM disappeared [OR (95% CI) = 0.76 (0.55, 1.06), p = 0.101]. In addition, our study found no proof to support the assumption that VDBP level was related to GDM risk causally [OR (95% CI) = 0.98 (0.93, 1.03), p = 0.408]. Conclusions: According to this study, a weak negative causal association between 25(OH)D and GDM risk was found, while we had little proof to support the link between VDBP and GDM. To further explore whether total or free 25(OH)D levels and GDM are causally related, GWAS data with an emphasis on women of reproductive age and other ethnic groups are required.

show abstract

CYP2E1 C-1054T and 96-bp I/D genetic variations and risk of gestational diabetes mellitus in chinese women: a case-control study

Cited by 3 publications

References 46 publications

Multigenerational diabetes mellitus

Multigenerational diabetes mellitus

Evidence for causal effects of polycystic ovary syndrome on oxidative stress: a two-sample mendelian randomisation study

25-Hydroxyvitamin D, Vitamin D Binding Protein and Gestational Diabetes Mellitus: A Two-Sample Mendelian Randomization Study

Contact Info

Product

Resources

About