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 4 publications

(1 citation statement)

References 46 publications

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“…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.

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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.

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Section: Subsectionsmentioning

confidence: 99%

Multigenerational diabetes mellitus

Thornton,

Shah,

Lillycrop

et al. 2024

Front. Endocrinol.

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

2023

BMC Med Genomics

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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.

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Association of iron homeostasis-related gene polymorphisms with pregnancy and neonatal outcomes in patients with gestational diabetes mellitus

Chen,

Huang,

et al. 2024

PLoS ONE

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Objective The purpose of this study was to assess associations between iron homeostasis-related gene polymorphisms and gestational diabetes mellitus (GDM), adverse pregnancy outcomes, and neonatal outcomes. Methods In total, 138 patients with GDM and 74 normal pregnancy controls were recruited. Time-of-flight mass spectrometry was used to genotype single-nucleotide polymorphisms (H63D rs1799945, TMPRSS6 rs855791, GDF15 rs1059369, rs4808793, BMP2 rs173107, C282Y rs3811647, rs1800562, rs269853, TF rs8177240, TFR2 rs7385804, FADS2 rs174577, and CUBN rs10904850) in 12 candidate genes related to iron homeostasis. Adverse pregnancy outcomes and neonatal health data were collected. Differences in genotype distributions and allele frequencies between patients and controls as well as their correlations with clinical factors were assessed. Additionally, associations between genotype, haemoglobin levels, and ferritin levels were evaluated. Results Pregnant women carrying the GDF15 rs4808793 allele (C) or TMPRSS6 rs855791 homozygous mutation (GG) had a significantly higher risk of GDM than that in the control group (p < 0.05). In patients with GDM, the BMP2 rs173107 heterozygous mutation (AC) was associated with significantly higher haemoglobin levels in late pregnancy compared with those for wild-type (AA) BMP2 (p < 0.05). Furthermore, in patients with GDM, the FADS2 rs174577 heterozygous mutation (AC) was associated with a significantly reduced risk of preterm birth (p < 0.05), the H63D rs1799945 heterozygous mutation (CG) was associated with a significantly increased risk of adverse neonatal outcomes (p < 0.05), TFR2 rs7385804 was associated a significantly reduced probability of caesarean section (p < 0.05), and the G mutation in TMPRSS6 rs855791 was related to a significantly increased probability of caesarean section (p < 0.05). Conclusions These results suggest that polymorphisms in genes related to iron metabolism could potentially impact pregnancy and neonatal outcomes in patients with GDM. Large-scale studies are needed to further clarify the relationship between these polymorphisms and susceptibility to GDM.

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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 4 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

Association of iron homeostasis-related gene polymorphisms with pregnancy and neonatal outcomes in patients with gestational diabetes mellitus

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