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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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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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Associations between two single nucleotide polymorphisms of the adiponectin gene, its circulating concentrations and cardiometabolic risk factors in prepubertal children with and without abdominal obesity.
Galcheva, SV, Martorana, D, Iotova, VM, Yotov, Y, Neri, TM, Street, ME
Journal of endocrinological investigation. 2013;(10):869-75
Abstract
BACKGROUND The adiponectin gene has been identified as a susceptibility locus for metabolic syndrome, diabetes and cardiovascular disease. AIM: To examine the influence of two single nucleotide polymorphisms (SNPs) of this gene (+276G>T and +45T>G) on circulating adiponectin concentrations, and to evaluate their relationship with adiposity and cardiometabolic risk factors in prepubertal children with and without abdominal obesity. MATERIAL AND METHODS 168 children (78M, 6-10 yr) were examined, divided into three groups based on waist circumference (WC). Auxological and biochemical parameters were measured by standard procedures. Adiponectin SNPs were genotyped using TaqMan allelic discrimination assays. RESULTS Adiponectin concentration correlated inversely with measures of adiposity (rBMIz-score=-0.211, pBMIz-score=0.007; rwc=-0.210, pwc=0.008; rwc/height=-0.215, pwc/height=0.006), and was significantly influenced by blood glucose, insulin and systolic blood pressure (SBP). The +276T-allele carriers had higher SBP and diastolic BP compared to GG-homozygotes (p<0.05), and expressed higher obesity-related measures and lower adiponectin concentrations. As to the +45T>G SNP, the GGsubject had higher total cholesterol and LDL-C concentrations compared to the T-allele carriers (p<0.05), showing worse obesity measures, higher triglyceride, glucose and insulin and lower serum adiponectin values. CONCLUSION Genetic variants of the adiponectin gene had an impact on adiposity, adiponectin concentrations and some cardiometabolic variables among prepubertal children.
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Polymorphisms of the LEP- and LEPR genes, metabolic profile after prolonged clozapine administration and response to the antidiabetic metformin.
Fernández, E, Carrizo, E, Fernández, V, Connell, L, Sandia, I, Prieto, D, Mogollón, J, Valbuena, D, Fernández, I, de Baptista, EA, et al
Schizophrenia research. 2010;(1-3):213-7
Abstract
BACKGROUND The role of leptin in atypical antipsychotic-induced metabolic dysfunction was explored by assessing the anthropometric and metabolic profile and the response to metformin (MET) of clozapine- (CLZ) treated schizophrenia patients according to their single nucleotide polymorphisms (SNPs) in the leptin promoter (LEP2548/GA) and leptin receptor (LEPR Q223R) genes. METHODS Phase 1. Body mass index (BMI), waist circumference, serum glucose, HbA1C, lipids, leptin, cortisol, insulin resistance index (HOMA-IR), metabolic syndrome and the frequencies of SNPs were assessed in 56 CLZ-treated patients (78.6% males). Phase 2. Fifty two phase 1 subjects were randomly assigned to MET XR (n=23) (1000 mg/day) or placebo (n=29) for 14 weeks. Changes in anthropometric and biochemical variables were compared between the SNPs. RESULTS Phase 1. The QQ group displayed the lowest triglyceride levels (p<0.05). No other significant difference was observed. Phase 2. Change in anthropometric variables did not differ between the genotypes in any treatment group. After MET, glucose levels significantly increased in the GG group (p<0.05), whereas the HOMA-IR and the low density cholesterol significantly decreased in the QQ- but not in the (QR+RR) group (p<0.05). No differences were observed after placebo. CONCLUSIONS BW response to CLZ was not related to LEP- and LEPR-SNPs. The GG and (QR+RR) genotypes showed an unexpectedly opposite and blunted response to MET administration respectively.
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Interaction of single nucleotide polymorphisms in ADRB2, ADRB3, TNF, IL6, IGF1R, LIPC, LEPR, and GHRL with physical activity on the risk of type 2 diabetes mellitus and changes in characteristics of the metabolic syndrome: The Finnish Diabetes Prevention Study.
Kilpeläinen, TO, Lakka, TA, Laaksonen, DE, Mager, U, Salopuro, T, Kubaszek, A, Todorova, B, Laukkanen, O, Lindström, J, Eriksson, JG, et al
Metabolism: clinical and experimental. 2008;(3):428-36
Abstract
Single nucleotide polymorphisms (SNPs) in the ADRB2, ADRB3, TNF, IL6, IGF1R, LIPC, LEPR, and GHRL genes were associated with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes mellitus (T2D) in the Finnish Diabetes Prevention Study (DPS). In this study, we determined whether polymorphisms in these genes modified the effect of changes in physical activity (PA) on the risk of T2D in the DPS. Moreover, we assessed whether the polymorphisms modified the effect of changes in PA on changes in measures of body fat, serum lipids, and blood pressure during the first year of the follow-up of the DPS. Overweight subjects with IGT (n = 487) were followed for an average of 4.1 years, and PA was assessed annually with a questionnaire. The interactions of the polymorphisms with changes in total and moderate-to-vigorous PA on the conversion to T2D during the 4.1-year follow-up were assessed using Cox regression with adjustments for the other components of the intervention (dietary changes, weight reduction). Univariate analysis of variance was used to assess interactions on changes in continuous variables during the first year of the follow-up. No interaction between the polymorphisms and PA on the conversion to T2D was found. The Leu72Met (rs696217) polymorphism in GHRL modified the effect of moderate-to-vigorous PA on changes in weight and waist circumference, the -501A/C (rs26802) polymorphism in GHRL modified the effect of total and moderate-to-vigorous PA on change in high-density lipoprotein cholesterol, and the Lys109Arg (rs1137100) polymorphism in LEPR modified the effect of total PA on change in blood pressure. In conclusion, genetic variation may modify the magnitude of the beneficial effects of PA on characteristics of the metabolic syndrome in persons with IGT.
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The genetic variation in the tenomodulin gene is associated with serum total and LDL cholesterol in a body size-dependent manner.
Tolppanen, AM, Pulkkinen, L, Kuulasmaa, T, Kolehmainen, M, Schwab, U, Lindström, J, Tuomilehto, J, Uusitupa, M, Kuusisto, J
International journal of obesity (2005). 2008;(12):1868-72
Abstract
We have reported that the sequence variation in the tenomodulin (TNMD) gene is associated with the risk of type 2 diabetes (T2DM), central obesity and serum levels of systemic immune mediators in the Finnish Diabetes Prevention Study (DPS), which is a longitudinal lifestyle intervention study on 522 middle-aged persons with impaired glucose tolerance (IGT). The aim of this study was to investigate whether the association with T2DM, observed in the DPS could be replicated in a larger, cross-sectional population-based random sample of 5298 men (3020 with normoglycaemia, 984 with impaired fasting glucose, 436 with IGT and 811 with T2DM) from the region of Kuopio, eastern Finland. To further explore the putative mechanisms linking TNMD to T2DM and metabolic syndrome, we studied the associations of TNMD sequence variation with lipid abnormalities characteristic to metabolic syndrome. The association with T2DM risk was not replicated, but significant associations were found with serum low-density lipoprotein and total cholesterol in a body mass index-dependent manner. These associations were also observed in the men of DPS, whereas in women these associations were not significant. These results from two independent study populations suggest that the genetic variation in TNMD could modulate cholesterol metabolism in obese men.