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Estrogen receptor ? gene polymorphism and vascular complications in girls with type 1 diabetes mellitus.

ABSTRACT: The effect of estrogens is mediated by activation of estrogen receptors (ERs). Because ER-? gene polymorphisms may exert different effects in childhood, we analyzed the associations between the IVS1 -397T>C (PvuII) polymorphism and systemic inflammatory state, proangiogenic factors, frequency of monocyte subsets, lipid profile, blood pressure, and vascular complications in girls with type 1 diabetes mellitus (DM1). We examined 180 young girls with DM1 and 120 healthy age-matched controls. The analysis concerned PvuII polymorphism of the ER-? gene as well as the levels of serum inflammatory markers (CRP, IL-6, TNF-?), proangiogenic factors (VEGF, angiogenin), 17?-estradiol, values of monocyte subsets (CD14++CD16- and CD14+CD16+), lipid profile, and blood pressure. In our study, girls with CC genotype had lower level of inflammatory and angiogenic factors and lower frequencies of CD14+CD16+ monocytes in comparison to CT or TT carriers. Simultaneously, the CC carriers had a greater population of CD14++CD16- monocytes, increased blood pressure, and serum levels of: estrogen, total cholesterol, triglycerides, and low-density lipoprotein cholesterol than girls bearing CT or TT genotype. Our study suggests a pleiotropic effect of PvuII polymorphic CC variant on diabetic vasculopathies. Although the CC genotype carriers demonstrate less inflammatory and angiogenic activity, they seem to display less favorable cardiometabolic features. Based on our study, we cannot distinguish PvuII ER-? genotype that could be useful in identification of DM1 girls that are more prone to develop of late vascular complications, before the occurrence of first clinical symptoms.

SUBMITTER: Slominski B

PROVIDER: S-EPMC5752735 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Estrogen receptor α gene polymorphism and vascular complications in girls with type 1 diabetes mellitus.

Słomiński Bartosz B Myśliwska Jolanta J Ryba-Stanisławowska Monika M Skrzypkowska Maria M Myśliwiec Małgorzata M

Molecular and cellular biochemistry 20170620 1-2

The effect of estrogens is mediated by activation of estrogen receptors (ERs). Because ER-α gene polymorphisms may exert different effects in childhood, we analyzed the associations between the IVS1 -397T>C (PvuII) polymorphism and systemic inflammatory state, proangiogenic factors, frequency of monocyte subsets, lipid profile, blood pressure, and vascular complications in girls with type 1 diabetes mellitus (DM1). We examined 180 young girls with DM1 and 120 healthy age-matched controls. The an ...[more]

PMID: 28634856

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Project description:PurposePeripheral vascular disease (PVD) is a life-threatening condition affecting the lower extremities. Common risk factors include type 2 diabetes (T2D), hypertension, dyslipidemia, smoking, and older age. There is a little-documented research on the genetic basis of the disease in Taiwan. We examined the impact of T2D and the blood pressure-associated rs17367504 variant of the Methylenetetrahydrofolate reductase (MTHFR) gene on PVD risk.Materials and methodsIn this population-based association study, we linked data from 8992 participants in Taiwan Biobank (TWB) to their medical records in the National Health Insurance Research Database (NHIRD). Participants were 30 to 70 years old at recruitment and included those assessed between 2008 and 2015. We tested for association of PVD with rs17367504 and T2D using multiple logistic regression models. The rs17367504 variant was assessed using the Axiom-Taiwan Biobank Array Plate (TWB chip: Affymetrix, Inc., Santa Clara, CA, USA).ResultsAmong cases with T2D (n = 1294), 158 (12.21%) were identified with PVD. T2D was associated with PVD (odds ratio [OR], 1.52; 95% confidence interval [CI], 1.21-1.91; p<0.001) whereas rs17367504 variant was not (OR, 0.96; CI, 0.76-1.21; p = 0.728 in AG/GG compared to AA homozygotes). However, T2D and rs17367504 had an interactive effect on PVD (p for interaction = 0.0076). Results from our stratified analyses displayed OR of 1.75 (CI, 1.35-2.26; p<0.001) in AA individuals with DM and 0.94 (CI, 0.56-1.58; p = 0.811) in AG+GG individuals with T2D. Using the AA genotype and no T2D as the reference group, the respective OR of PVD was 1.77 (CI, 1.38-2.28; p<0.001) in AA individuals with T2D; 1.18 (CI, 0.91-1.55; p = 0.215) in AG+GG individuals with no T2D, and 1.03 (CI, 0.66-1.60; p = 0.892) in AG+GG individuals with T2D .ConclusionWe found that type 2 diabetes was associated with increased risk of peripheral vascular disease, particularly in AA genotype carriers of the rs17367504 variant in Taiwan.

Dataset Information

Estrogen receptor ? gene polymorphism and vascular complications in girls with type 1 diabetes mellitus.

Publications

Estrogen receptor α gene polymorphism and vascular complications in girls with type 1 diabetes mellitus.

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