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Diverse Associations of Plasma Selenium Concentrations and SELENOP Gene Polymorphism with Metabolic Syndrome and Its Components.
Zhou, L, Luo, C, Yin, J, Zhu, Y, Li, P, Chen, S, Sun, T, Xie, M, Shan, Z, Cao, B, et al
Oxidative medicine and cellular longevity. 2020;:5343014
Abstract
The relationship between selenium and metabolic syndrome (MetS) has been discussed controversially, and limited studies have examined the associations of single nucleotide polymorphisms in selenoproteins genes with MetS. Hence, to examine the associations of plasma selenium concentrations and selenoprotein P rs7579 polymorphism with MetS, a case-control study of 1279 MetS cases and 1279 sex- and age- (±2 years) matched controls was conducted based on the baseline data of the Tongji-Ezhou Cohort study. Plasma selenium concentrations were measured by inductively coupled plasma mass spectrometry. MetS was defined using the definition of the Joint Interim Statement, adjusted for the Chinese population. In addition, the rs7579 polymorphism was genotyped by the Agena MassARRAY System. Plasma selenium concentrations in the MetS group were higher than in the control group (93.88 μg/L (83.17-107.41) vs. 92.66 μg/L (82.36-103.53), P < 0.05). Compared with quartile 4 (≥103.53 μg/L), the multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) associated with MetS were 0.79 (0.59-1.06) for quartile 1 (<82.36 μg/L), 0.75 (0.56-1.01) for quartile 2 (82.37-92.66 μg/L), and 0.61 (0.45-0.83) for quartile 3 (92.67-103.52 μg/L). The cubic spline analyses revealed a U-shaped association between plasma selenium and MetS, with the lowest risk at around 93.69 μg/L. Moreover, in cubic spline analyses, plasma selenium showed U-shaped associations with central obesity and high blood pressure, positive associations with hypertriglyceridemia and hyperglycemia, and a negative association with low high-density lipoprotein cholesterol. Additionally, both the GA and GA+AA genotype carriers were associated with increased ORs of MetS comparing with the GG genotype carriers. Our findings suggested a U-shaped association between plasma selenium and MetS and diverse associations between plasma selenium and components of MetS. Furthermore, our study found that the A allele of rs7579 was associated with higher odds of MetS. Further studies are needed to confirm our findings and elucidate the underlying mechanisms.
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PPARG and FTO polymorphism can modulate the outcomes of a central European diet and a Mediterranean diet in centrally obese postmenopausal women.
Chmurzynska, A, Muzsik, A, Krzyżanowska-Jankowska, P, Mądry, E, Walkowiak, J, Bajerska, J
Nutrition research (New York, N.Y.). 2019;:94-100
Abstract
The aim of this study was to test the hypothesis that polymorphism of genes with the biggest effects on body mass (FTO and PPARG) can affect the results of dieting in centrally obese postmenopausal women. A total of 144 volunteers were randomized to a 16-week intervention with two hypocaloric diets: either a Mediterranean diet (MED) moderate in fat (37% total energy as fat) or the Central European diet (CED) moderate in carbohydrates (55% total energy as carbohydrates). The associations between FTO and PPARG polymorphism on the baseline body mass, body composition, blood pressure, lipid and non-lipid parameters, and their changes after the trial were analyzed. None of the examined baseline outcomes differed in the rs9939609 FTO subgroups; abdominal fat was higher in the minor (G) allele carriers of the PPARG rs1801282. After the intervention, in the CED group, the PPARG G allele carriers showed greater reductions in weight (-6.58 ± 0.61 vs -9.58 ± 0.83; P < .01), lean mass (-0.38 ± 0.29 vs -1.79 ± 0.38; P < .05) and high-density lipoprotein (HDL) cholesterol (-0.46 ± 0.77 vs -5.25 ± 1.49; P < .01) than the CC homozygotes, and the TT individuals of the rs9939609 FTO had greater reductions in diastolic blood pressure (-9.03 ± 1.78 vs. -7.58 ± 1.50; P < .05). In the MED group, greater reductions in abdominal fat were observed in the G allele carriers than in the CC homozygotes (-3.31 ± 0.26 vs. -4.23 ± 0.41; P < .05). PPARG and FTO polymorphism may affect the outcomes of the diets aimed at weight reduction in postmenopausal women.
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Genome-wide association analysis of common genetic variants of resistant hypertension.
El Rouby, N, McDonough, CW, Gong, Y, McClure, LA, Mitchell, BD, Horenstein, RB, Talbert, RL, Crawford, DC, , , Gitzendanner, MA, et al
The pharmacogenomics journal. 2019;(3):295-304
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Abstract
Resistant hypertension (RHTN), defined as uncontrolled blood pressure (BP) ≥ 140/90 using three or more drugs or controlled BP (<140/90) using four or more drugs, is associated with adverse outcomes, including decline in kidney function. We conducted a genome-wide association analysis in 1194 White and Hispanic participants with hypertension and coronary artery disease from the INternational VErapamil-SR Trandolapril STudy-GENEtic Substudy (INVEST-GENES). Top variants associated with RHTN at p < 10-4 were tested for replication in 585 White and Hispanic participants with hypertension and subcortical strokes from the Secondary Prevention of Subcortical Strokes GENEtic Substudy (SPS3-GENES). A genetic risk score for RHTN was created by summing the risk alleles of replicated RHTN signals. rs11749255 in MSX2 was associated with RHTN in INVEST (odds ratio (OR) (95% CI) = 1.50 (1.2-1.8), p = 7.3 × 10-5) and replicated in SPS3 (OR = 2.0 (1.4-2.8), p = 4.3 × 10-5), with genome-wide significance in meta-analysis (OR = 1.60 (1.3-1.9), p = 3.8 × 10-8). Other replicated signals were in IFLTD1 and PTPRD. IFLTD1 rs6487504 was associated with RHTN in INVEST (OR = 1.90 (1.4-2.5), p = 1.1 × 10-5) and SPS3 (OR = 1.70 (1.2-2.5), p = 4 × 10-3). PTPRD rs324498, a previously reported RHTN signal, was among the top signals in INVEST (OR = 1.60 (1.3-2.0), p = 3.4 × 10-5) and replicated in SPS3 (OR = 1.60 (1.1-2.4), one-sided p = 0.005). Participants with the highest number of risk alleles were at increased risk of RHTN compared to participants with a lower number (p-trend = 1.8 × 10-15). Overall, we identified and replicated associations with RHTN in the MSX2, IFLTD1, and PTPRD regions, and combined these associations to create a genetic risk score.
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Single nucleotide polymorphisms at the ADIPOQ gene locus rs1501299 interact with different type of dietary fatty acids in two hypocaloric diets.
de Luis, DA, Izaola, O, Primo, D, Aller, R
European review for medical and pharmacological sciences. 2019;(7):2960-2970
Abstract
OBJECTIVE Some adiponectin gene (ADIPOQ) and single nucleotide polymorphisms (SNPs) have been related to adiponectin levels and metabolic parameters. Few studies of interaction gene-nutrient have been realized in this topic area. The aim of our study was to analyze the effect of the rs1501299 ADIPOQ gene polymorphism, and the dietary intake on total adiponectin levels and the insulin resistance changes after an enriched-monounsaturated fat (Diet M) vs. an enriched-polyunsaturated fat hypocaloric diet (Diet P). PATIENTS AND METHODS A Caucasian population of 363 obese patients was enrolled in a randomized clinical trial with two hypocaloric diets. Before and after 12 weeks on each hypocaloric diet, an anthropometric evaluation, an assessment of nutritional intake and a biochemical analysis were realized. The statistical analysis was performed for the combined GT and TT as a group (mutant) and GG as second group (wild). RESULTS With both caloric restriction strategies, body weight, body mass index (BMI), fat mass, waist circumference, systolic blood pressure and leptin levels decreased. After Diet P, only subjects with GG genotype showed a significant improvement in the insulin levels (GG vs. GT±TT) (-3.2±1.0 mU/L vs. -0.6±0.4 mU/L: p=0.01) and in the homeostasis model assessment (HOMA-IR) (-1.1±0.2 units vs. -0.3±0.4 units: p=0.02). The same improvement in both parameters was reported after Diet M: insulin levels (-3.7±0.9 mU/L vs. -0.4±0.5 mU/L: p=0.01) and HOMA-IR (-1.0±0.2 units vs. -0.4±0.3 units: p=0.03). After weight loss with diet M, both genotypes (GG vs. GT±TT) showed similar decrease in total cholesterol and LDL-cholesterol. Only subjects with GG genotype showed a significant increase of the adiponectin levels after both diets: (Diet P: 9.3±3.0 ng/dl vs. Diet M: 8.2±2.9 ng/dl: p=0.38). CONCLUSIONS The GG genotype of ADIPOQ gene variant (rs1501299) is associated to a significant improvement in the adiponectin levels and a decrease of insulin and HOMA-IR after two different hypocaloric diets with different profile of unsaturated dietary fats.
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Common polymorphism in the cannabinoid receptor gene type 2 (CB2R) rs3123554 are associated with metabolic changes after two different hypocaloric diets with different dietary fatty profiles.
Aller, R, Primo, D, Izaola, O, de Luis, DA
Clinical nutrition (Edinburgh, Scotland). 2019;(6):2632-2638
Abstract
BACKGROUND The role of CB2R gene variants on weight loss after a dietary intervention has been investigated in few studies. OBJECTIVE We evaluate the effect of this genetic variant (rs3123554) of CB2R gene on cardiovascular risk factors and weight loss secondary to high monounsaturated fat vs a high polyunsaturated fat hypocaloric diets. DESIGN A Caucasian population of 362 obese patients was enrolled. Patients were randomly allocated during 3 months to one of two diets (Diet P high polyunsaturated (PUFAs) fat hypocaloric diet vs, Diet M high monounsaturated (MUFAs) fat hypocaloric diet). RESULTS In both genotype groups (GG vs GA+AA), body weight, body mass index (BMI), fat mass, waist circumference and systolic blood pressure decreased after diet P and M. Body weight, BMI, fat mass and waist circumference were higher in A allele carriers than non A allele carriers. The improvement of these parameters was higher in non A allele carriers than A allele carriers. In non A allele carriers with both diets, the decrease of total cholesterol, LDL-cholesterol, insulin and HOMA-IR was higher than A allele carriers after both diets. After diet P, triglyceride levels decrease in non A allele carriers. CONCLUSION Our data suggest that carriers of the minor allele of rs3123554 variant of CB2R gene lose less body weight during to different hypocaloric diets with different fatty acid. Moreover, non A-allele carriers showed a better response of LDL-cholesterol, HOMA-IR and insulin levels than A-carriers with both hypocaloric diets.
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Triacylglycerol-Lowering Effect of Docosahexaenoic Acid Is Not Influenced by Single-Nucleotide Polymorphisms Involved in Lipid Metabolism in Humans.
AbuMweis, SS, Panchal, SK, Jones, PJH
Lipids. 2018;(9):897-908
Abstract
The triacylglycerol (TAG)-lowering effects of long-chain n-3 fatty acids, and in particular docosahexaenoic acid (DHA), are well documented, although these effects manifest large interindividual variability. The objective of this secondary analysis is to investigate whether common single-nucleotide polymorphisms (SNP) in genes involved in DHA synthesis and TAG metabolism are associated with the responsiveness of blood lipids, lipoprotein, and apolipoprotein concentration to dietary treatment by DHA supplied in high-oleic canola oil (HOCO). In a randomized, crossover-controlled feeding trial, 129 subjects with metabolic syndrome received high-oleic canola oil (HOCO) and high-oleic canola oil supplemented with DHA (HOCO-DHA), each for 4 weeks. During the HOCO-DHA phase, the intake of DHA ranged from 1 to 2.5 g/day. The subjects were genotyped for apolipoprotein E (APOE) isoforms, and SNP including FADS1-rs174561, FADS2-rs174583, ELOVL2-rs953413, ELOVL5-rs2397142, CETP-rs5882, SCD1-rs2234970, PPARA-rs6008259, and LIPF-rs814628 were selected as important genes controlling fatty acid metabolism. Overall, consumption of HOCO-DHA oil reduced blood concentrations of TAG by 24% compared to HOCO oil. The reduction in TAG was independent of genetic variations in the studied genes. Similarly, no treatment-by-gene interactions were evident in the response to other lipids, lipoproteins, or apolipoproteins to DHA supplementation. Nevertheless, a lower interindividual variation in the TAG response to DHA supplementation compared to other studies was observed in this analysis. The TAG-lowering effect of a supplemental body-weight-based dose of DHA was not influenced by genetic variations in APOE, FADS1, FADS2, ELOVL2, ELOVL5, CETP, SCD1, PPARA, and LIPF.
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Influence of FTO rs9939609 and Mediterranean diet on body composition and weight loss: a randomized clinical trial.
Di Renzo, L, Cioccoloni, G, Falco, S, Abenavoli, L, Moia, A, Sinibaldi Salimei, P, De Lorenzo, A
Journal of translational medicine. 2018;(1):308
Abstract
BACKGROUND The Mediterranean diet (MeD) plays a key role in the prevention of obesity. Among the genes involved in obesity, the Fat mass and obesity-associated gene (FTO) is one of the most known, but its interaction with MeD remained uncertain so far. METHODS We carried out a study on a sample of 188 Italian subjects, analyzing their FTO rs9939609 alleles, and the difference in body composition between the baseline and a 4-weeks nutritional intervention. The sample was divided into two groups: the control group of 49 subjects, and the MeD group of 139 subjects. RESULTS We found significant relations between MeD and both variation of total body fat (ΔTBFat) (p = 0.00) and gynoid body fat (p = 0.04). ∆TBFat (kg) demonstrated to have a significant relation with the interaction diet-gene (p = 0.04), whereas FTO was associated with the variation of total body water (p = 0.02). CONCLUSIONS MeD demonstrated to be a good nutritional treatment to reduce the body fat mass, whereas data about FTO remain uncertain. Confirming or rejecting the hypothesis of FTO and its influence on body tissues during nutritional treatments is fundamental to decide whether its effect has to be taken into consideration during both development of dietetic plans and patients monitoring. Trial Registration ClinicalTrials.gov Id: NCT01890070. Registered 01 July 2013, https://clinicaltrials.gov/ct2/show/NCT01890070.
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The Single Nucleotide Polymorphism PPARG2 Pro12Ala Affects Body Mass Index, Fat Mass, and Blood Pressure in Severely Obese Patients.
Rodrigues, APDS, Rosa, LPS, da Silva, HD, Silveira-Lacerda, EP, Silveira, EA
Journal of obesity. 2018;:2743081
Abstract
BACKGROUND The PPARG2 Pro12Ala (rs1801282) and IL6 -174G >C (rs1800795) have important function in body weight regulation and a potential role in obesity risk. We aimed to investigate the association between PPARG2 Pro12Ala and IL6 -174G >C variants and the genotypes interaction with body composition, metabolic markers, food consumption, and physical activity in severely obese patients. METHODS 150 severely obese patients (body mass index (BMI) ≥ 35 kg/m2) from Central Brazil were recruited. Body composition, metabolic parameters, physical activity, and dietary intake were measured. The genotype was determined by the qPCR TaqMan Assays System. Multiple linear regression and multiple logistic regression models were fitted adjusting for confounders. RESULTS Ala carriers of the Pro12Ala polymorphism had higher adiposity measures (BMI: p=0.031, and fat mass: p=0.049) and systolic blood pressure (p=0.026) compared to Pro homozygotes. We found no important associations between the -174G >C polymorphism and obesity phenotypes. When genotypes were combined, individuals with genotypes ProAla + AlaAla and GC + CC presented higher BMI (p=0.029) and higher polyunsaturated fatty acids (PUFAs) consumption (p=0.045) compared to the ones with genotypes ProPro and GG, and individuals carriers of the PPARG2 Ala allele only (genotype ProAla + AlaAla and GG) had higher fat mass and systolic and diastolic blood pressure compared to the ones with genotypes ProPro and GG. CONCLUSIONS Severely obese individuals carrying the Ala allele of the PPARG2 Pro12Ala polymorphism had higher measures of adiposity and blood pressure, while no important associations were found for the IL6 -174G >C polymorphism.
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No clear support for a role for vitamin D in Parkinson's disease: A Mendelian randomization study.
Larsson, SC, Singleton, AB, Nalls, MA, Richards, JB, ,
Movement disorders : official journal of the Movement Disorder Society. 2017;(8):1249-1252
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BACKGROUND Observational studies have found that relative to healthy controls, patients with Parkinson's disease have lower circulating concentrations of 25-hydroxyvitamin D, a clinical biomarker of vitamin D status. However, the causality of this association is uncertain. We undertook a Mendelian randomization study to investigate whether genetically decreased 25-hydroxyvitamin D concentrations are associated with PD to minimize confounding and prevent bias because of reverse causation. METHODS As instrumental variables for the Mendelian randomization analysis, we used 4 single-nucleotide polymorphisms that affect 25-hydroxyvitamin D concentrations (rs2282679 in GC, rs12785878 near DHCR7, rs10741657 near CYP2R1, and rs6013897 near CYP24A1). Summary effect size estimates of the 4 single-nucleotide polymorphisms on PD were obtained from the International Parkinson's Disease Genomics Consortium (including 5333 PD cases and 12,019 controls). The estimates of the 4 single-nucleotide polymorphisms were combined using an inverse-variance weighted meta-analysis. RESULTS Of the 4 single-nucleotide polymorphisms associated with 25-hydroxyvitamin D concentrations, one (rs6013897 in CYP24A1) was associated with PD (odds ratio per 25-hydroxyvitamin D-decreasing allele, 1.09; 95% confidence interval, 1.02-1.16; P = 0.008), whereas no association was observed with the other 3 single-nucleotide polymorphisms (P > 0.23). The odds ratio of PD per genetically predicted 10% lower 25-hydroxyvitamin D concentration, based on the 4 single-nucleotide polymorphisms, was 0.98 (95% confidence interval, 0.93-1.04; P = 0.56). CONCLUSIONS This Mendelian randomization study provides no clear support that lowered 25-hydroxyvitamin D concentration is causally associated with risk of PD. © 2017 International Parkinson and Movement Disorder Society.
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Autophagy-related polymorphisms predict hypertension in patients with metastatic colorectal cancer treated with FOLFIRI and bevacizumab: Results from TRIBE and FIRE-3 trials.
Berger, MD, Yamauchi, S, Cao, S, Hanna, DL, Sunakawa, Y, Schirripa, M, Matsusaka, S, Yang, D, Groshen, S, Zhang, W, et al
European journal of cancer (Oxford, England : 1990). 2017;:13-20
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Abstract
PURPOSE The most frequent bevacizumab-related side-effects are hypertension, proteinuria, bleeding and thromboembolism. To date, there is no biomarker that predicts anti-VEGF-associated toxicity. As autophagy inhibits angiogenesis, we hypothesised that single-nucleotide polymorphisms (SNPs) within autophagy-related genes may predict bevacizumab-mediated toxicity in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS Patients with mCRC treated with first-line FOLFIRI and bevacizumab in two phase III randomised trials, namely the TRIBE trial (n = 219, discovery cohort) and the FIRE-3 trial (n = 234, validation cohort) were included in this study. Patients receiving treatment with FOLFIRI and cetuximab (FIRE-3, n = 204) served as a negative control. 12 SNPs in eight autophagy-related genes (ATG3/5/8/13, beclin 1, FIP200, unc-51-like kinase 1, UVRAG) were analysed by PCR-based direct sequencing. RESULTS The FIP200 rs1129660 variant showed significant associations with hypertension in the TRIBE cohort. Patients harbouring any G allele of the FIP200 rs1129660 SNP showed a significantly lower rate of grade 2-3 hypertension compared with the A/A genotype (3% versus 15%, odds ratio [OR] 0.17; 95% confidence interval [CI], 0.02-0.73; P = 0.009). Similarly, G allele carriers of the FIP200 rs1129660 SNP were less likely to develop grade 2-3 hypertension than patients with an A/A genotype in the FIRE-3 validation cohort (9% versus 20%, OR 0.43; 95% CI, 0.14-1.11; P = 0.077), whereas this association could not be observed in the control cohort (12% versus 9%, OR 1.40; 95% CI, 0.45-4.04; P = 0.60). CONCLUSION This is the first report demonstrating that polymorphisms in the autophagy-related FIP200 gene may predict hypertension in patients with mCRC treated with FOLFIRI and bevacizumab.