Association of PPAR-γ2 and β3-AR Polymorphisms With Postmenopausal Hypertension.
Ontology highlight
ABSTRACT:
SUBMITTER: Grygiel-Gorniak B
PROVIDER: S-EPMC8032114 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Peroxisome proliferator-activated receptors (PPARs) play roles in glucose and lipid metabolism regulation. Pro12Ala PPAR-γ2 and +294T/C PPAR-δ have been associated with dyslipidemia, hyperglycemia and high body mass index (BMI). We compared metabolic traits and determined associations with Pro12Ala PPAR-γ2 or +294T/C PPAR-δ polymorphism among teenagers from different ethnicity. Four hundred and twelve samples with previous biochemical and biometric measurements were used. Genomic DNA from peripheral blood was extracted and analyzed by end-point PCR for Pro12Ala PPAR-γ2. The +294T/C PPAR-δ PCR product was also digested with Bsl I. Two genotype groups were formed: major allele homozygous and minor allele carriers. Pro12Ala PPAR-γ2 G minor allele frequencies were: 10% in Mestizo-1, 19% in Mestizo-2, 23% in Tarahumara, 12% in Mennonite, and 17% in the total studied population. The +294T/C PPAR-δ C minor allele frequencies were: 18% in Mestizo-1, 20% in Mestizo-2, 6% in Tarahumara, 13% in Mennonite, and 12% in the total studied population. Teenagers with PPAR-γ2 G allele showed a greater risk for either high waist/height ratio or low high-density lipoprotein; and, also had lower total cholesterol. Whereas, PPAR-γ2 G allele showed lower overweight/obesity phenotype (BMI Z-score) frequency, PPAR-δ C allele was a risk factor for it. Metabolic traits were associated with both PPAR polymorphisms.
| S-EPMC7397260 | biostudies-literature
Project description:Recently, we have observed two significant pandemics caused by communicable (COVID-19) and non-communicable factors (obesity). Obesity is related to a specific genetic background and characterized by immunogenetic features, such as low-grade systemic inflammation. The specific genetic variants include the presence of polymorphism of the Peroxisome Proliferator-Activated Receptors gene (PPAR-γ2; Pro12Ala, rs1801282, and C1431T, rs3856806 polymorphisms), β-adrenergic receptor gene (3β-AR; Trp64Arg, rs4994), and Family With Sequence Similarity 13 Member A gene (FAM13A; rs1903003, rs7671167, rs2869967). This study aimed to analyze the genetic background, body fat distribution, and hypertension risk in obese metabolically healthy postmenopausal women (n = 229, including 105 lean and 124 obese subjects). Each patient underwent anthropometric and genetic evaluations. The study has shown that the highest value of BMI was associated with visceral fat distribution. The analysis of particular genotypes has revealed no differences between lean and obese women except for FAM13A rs1903003 (CC), which was more prevalent in lean patients. The co-existence of the PPAR-γ2 C1431C variant with other FAM13A gene polymorphisms [rs1903003(TT) or rs7671167(TT), or rs2869967(CC)] was related to higher BMI values and visceral fat distribution (WHR > 0.85). The co-association of FAM13A rs1903003 (CC) and 3β-AR Trp64Arg was associated with higher values of systolic (SBP) and diastolic blood pressure (DBP). We conclude that the co-existence of FAM13A variants with C1413C polymorphism of the PPAR-γ2 gene is responsible for body fat amount and distribution.
| S-EPMC10137345 | biostudies-literature
Project description:BackgroundMounting evidence has suggested that α-adducin and G-protein β3 (GNB3) genes are logical candidates for salt-sensitive hypertension. Some, but not all, studies have reported that α-adducin G460T and GNB3 C825T polymorphisms may influence the risk of the disease. To comprehensively address this issue, we performed a meta-analysis to evaluate the influence of these two polymorphisms on hypertension and potential biases in Chinese.MethodsData were analyzed using Stata (v11.0) and random-effects model was applied irrespective of between-studies heterogeneity, which was evaluated via subgroup and meta-regression analyses. Study quality was assessed in duplicate. Publication bias was weighed using Egger's test and funnel plot.Results36 study populations totaling 9042 hypertensive patients and 8399 controls were finally identified. Overall, in allelic/genotypic/dominant/recessive models, no significant association was identified for both G460T and C825T polymorphisms (P>0.05) and there was possible heterogeneity (I(2)>25%). Subgroup analyses by study design indicated that the magnitude of association in population-based studies was marginally significantly strengthened for α-adducin G460T allelic model (OR = 1.12; 95% CI: 1:00-1.25; P = 0.043). Moreover, subgroup analyses by geographic distribution indicated comparison of 825T with 825C yielded a marginally significant increased risk in southern Chinese only (OR = 1.48; 95% CI: 1.01-2.16; P = 0.045). Further meta-regression analyses showed that geographic regions were a significant source of between-study heterogeneity for both polymorphisms. There was a possibility of publication bias for G460T, but not for C825T.ConclusionsOur overall results suggest null association of α-adducin G460T and GNB3 C825T polymorphisms with hypertension in Chinese but indicate local marginal significance of C825T, as a putative salt-sensitive switch, in southern Chinese.
| S-EPMC3045422 | biostudies-literature
Project description:The Pro12Ala (rs1801282) polymorphism in peroxisome proliferator-activated receptor-γ2 (PPAR-γ2) has been convincingly associated with insulin resistance (IR) and type 2 diabetes (T2D) among Europeans, in interaction with a high-fat diet. Mexico is disproportionally affected by obesity and T2D however, whether the Pro12Ala polymorphism is associated with early metabolic complications in this population is unknown. We assessed the association of PPAR-γ2 Pro12Ala with metabolic traits in 1457 Mexican children using linear regression models. Interactions between PPAR-γ2 Pro12Ala and circulating lipids on metabolic traits were determined by adding an interaction term to regression models. We observed a high prevalence of overweight/obesity (49.2%), dyslipidemia (34.9%) and IR (11.1%). We detected nominally significant/significant interactions between lipids (total cholesterol, HDL-cholesterol, LDL-cholesterol), the PPAR-γ2 Pro12Ala genotype and waist-to-hip ratio, fasting insulin, HOMA-IR and IR (9.30 × 10(-4) ≤ Pinteraction ≤ 0.04). Post-hoc subgroup analyses evidenced that the association between the PPAR-γ2 Pro12Ala genotype and fasting insulin, HOMA-IR and IR was restricted to children with total cholesterol or LDL-cholesterol values higher than the median (0.02 ≤ P ≤ 0.03). Our data support an association of the Pro12Ala polymorphism with IR in Mexican children and suggest that this relationship is modified by dyslipidemia.
| S-EPMC4830984 | biostudies-other
Project description:Immune cells infiltrate adipose tissues and provide a framework to regulate energy homeostasis. However, the precise underlying mechanisms and signaling by which the immune system regulates energy homeostasis in metabolic tissues remain poorly understood. Here, we show that the AT-rich interactive domain 5A (Arid5a), a cytokine-induced nucleic acid binding protein, is important for the maintenance of adipose tissue homeostasis. Long-term deficiency of Arid5a in mice results in adult-onset severe obesity. In contrast, transgenic mice overexpressing Arid5a are highly resistant to high-fat diet-induced obesity. Inhibition of Arid5a facilitates the in vitro differentiation of 3T3-L1 cells and fibroblasts to adipocytes, whereas its induction substantially inhibits their differentiation. Molecular studies reveal that Arid5a represses the transcription of peroxisome proliferator activated receptor gamma 2 (Ppar-γ2) due to which, in the absence of Arid5a, Ppar-γ2 is persistently expressed in fibroblasts. This phenomenon is accompanied by enhanced fatty acid uptake in Arid5a-deficient cells, which shifts metabolic homeostasis toward prolipid metabolism. Furthermore, we show that Arid5a and Ppar-γ2 are dynamically counterregulated by each other, hence maintaining adipogenic homeostasis. Thus, we show that Arid5a is an important negative regulator of energy metabolism and can be a potential target for metabolic disorders.
| S-EPMC6660722 | biostudies-literature
Project description:Habitual physical activity is understood to help prevent type 2 diabetes and atherosclerotic cardiovascular disease via beneficial effects on both metabolism and the vascular system. However, individuals do not have uniform cardiometabolic responses to physical activity. Here we explore the extent to which variation in the proliferator-activated receptor-alpha (PPAR?) gene, which modulates carbohydrate and lipid metabolism, vascular function, and inflammation, predicts the overall cardiometabolic risk (CMR) profile of individuals engaging in various levels of physical activity.917 unrelated, community volunteers (52% female, of Non-Hispanic European ancestry) aged 30-54 years, participated in the cross-sectional study. Subjects were genotyped for 5 single nucleotide polymorphisms in the PPAR? gene, from which common haplotypes were defined. A continuous measure of CMR was calculated as an aggregate of 5 traditional risk factors: waist circumference, resting blood pressure, fasting serum triglycerides, HDL-cholesterol and glucose. Regression models were used to examine the main and interactive effects of physical activity and genetic variation on CMR. One common PPAR? haplotype (H-23) was associated with a higher CMR. This association was moderated by daily physical activity (B = -0.11, SE = 0.053, t = -2.05, P = 0.04). Increased physical activity was associated with a steeper reduction of CMR in persons carrying the otherwise detrimental H-23 haplotype.Variations in the PPAR? gene appear to magnify the cardiometabolic benefits of habitual physical activity.
| S-EPMC4050124 | biostudies-literature
Project description:The beta-3 adrenergic receptor (β3-AR) is by far the least studied isotype of the beta-adrenergic sub-family. Despite its study being long hampered by the lack of suitable animal and cellular models and inter-species differences, a substantial body of literature on the subject has built up in the last three decades and the physiology of β3-AR is unraveling quickly. As will become evident in this work, β3-AR is emerging as an appealing target for novel pharmacological approaches in several clinical areas involving metabolic, cardiovascular, urinary, and ocular disease. In this review, we will discuss the most recent advances regarding β3-AR signaling and function and summarize how these findings translate, or may do so, into current clinical practice highlighting β3-AR's great potential as a novel therapeutic target in a wide range of human conditions.
| S-EPMC6523418 | biostudies-literature
Project description:BackgroundMultiple cross-sectional epidemiologic studies have suggested an association between periodontal disease and tooth loss and hypertension, but the temporality of these associations remains unclear. The objective of our study was to evaluate the association of baseline self-reported periodontal disease and edentulism with incident hypertension.MethodsStudy participants were 36,692 postmenopausal women in the Women's Health Initiative-Observational Study who were followed annually from initial periodontal assessment (1998-2003) through 2015 (mean follow-up 8.3 years) for newly diagnosed treated hypertension. Cox proportional hazards regression with adjustment for potential confounders was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsEdentulism was significantly associated with incident hypertension in crude (HR (95% CI) = 1.38 (1.28-1.49)) and adjusted (HR (95% CI) = 1.21 (1.11-1.30)) models. This association was stronger among those <60 years compared to ?60 years (P interaction 0.04) and among those with <120 mm Hg systolic blood pressure, compared to those with ?120 mm Hg (P interaction 0.004). No association was found between periodontal disease and hypertension.ConclusionsThese findings suggest that edentulous postmenopausal women may represent a group with higher risk of developing future hypertension. As such improved dental hygiene among those at risk for tooth loss as well as preventive measures among the edentulous such as closer blood pressure monitoring, dietary modification, physical activity, and weight loss may be warranted to reduce disease burden of hypertension. Further studies are needed to clarify these results and further elucidate a potential role of periodontal conditions on hypertension risk.
| S-EPMC6331709 | biostudies-literature
Project description:BackgroundRecent studies have reported better predictive performance of triglyceride glucose (TyG) index for cardiovascular events in women, however, whether this association persists in postmenopausal women is inconclusive. We investigated the association between TyG index and H-type hypertension (HHT) in postmenopausal women.Methods1,301 eligible women with hypertension were included in this cross-sectional study. Concomitant homocysteine levels >10 μmol/L were defined as H-type hypertension. The TyG index was calculated as ln [triglycerides (mg/dl) × fasting glucose (mg/dl)/2]. Multivariable logistic regression models and restricted cubic spline models were used to assess the association between TyG index and H-type hypertension in postmenopausal women, and subgroup analyses were performed for potential confounders.ResultsOf the 1,301 hypertensive patients, 634 (48.7%) participants had H-type hypertension. In each adjusted model, TyG index was significantly associated with the risk of H-type hypertension. each 1-unit increase in TyG index was associated with an increased risk of H-type hypertension in all participants (OR = 1.6; 95% CI, 1.3-2.0; P < 0.001), and there was a linear relationship between TyG index and H-type hypertension (P for linear trend < 0.001).ConclusionTyG index is positively associated with H-type hypertension in postmenopausal women, suggesting that TyG index may be a promising marker for H-type hypertension. By controlling lipid levels and blood glucose levels, it may help prevent H-type hypertension in postmenopausal women.
| S-EPMC10646504 | biostudies-literature
Project description:BACKGROUND:Both peroxisome activator proteins (PPARs) and fetuin-A play a role in lipid and glucose metabolism. AIMS:We investigated whether PPAR? intron 7 G2468/C and PPAR?2 Pro12Ala and PPAR? exon 6 C161T polymorphisms are associated with serum fetuin-A concentrations. PATIENTS AND METHODS:The PPAR? intron 7 G/C polymorphism was studied in cohort 1 (79 reference individuals, 165 postinfarction patients). The two PPAR? polymorphisms were investigated in cohort 2 (162 reference individuals, 165 postinfarction patients). Fetuin-A levels and PPAR polymorphisms were determined by radial immunodiffusion and polymerase chain reaction-restriction fragment length polymorphism techniques. RESULTS:The C allele variant of PPAR? intron 7 G2467C was associated with higher fetuin-A levels (p = 0.018). Postinfarction status (p = 0.001), PPAR? intron 7 GG/GC/CC genotypes (p = 0.032), and the C allele (p = 0.021) were the strongest determinants of fetuin-A concentration in a multiple regression model. Higher fetuin-A levels were associated with the Pro variant of PPAR?2 (p = 0.047). Postinfarction status (p = 0.041) and BMI (p < 0.001) but not PPAR?2 Pro were the strongest determinants of fetuin-A concentrations. PPAR? exon 6 C161T genotypes were not associated with fetuin-A levels. CONCLUSIONS:Fetuin-A was determined mainly by the PPAR? intron 7C allele and postinfarction status in cohort 1 and the BMI and postinfarction in cohort 2. The PPAR? intron 7C and PPAR?2 Pro variants are associated with fetuin-A levels.
| S-EPMC5525087 | biostudies-literature