Association study of candidate genes with obesity and metabolic traits in antipsychotic-treated patients with first-episode psychosis over a 2-year period

Aims: Patients with a first episode of psychosis (FEP) often display different metabolic disturbances even independently of drug therapy. However, antipsychotic (AP) treatment, especially with second-generation APs, is strongly linked to weight gain, which increases patients’ risk of developing obesity and other metabolic diseases. There is an important genetic risk component that can contribute to the appearance of these disturbances. The aim of the present study was to evaluate the effect of polymorphisms in selected candidate genes on obesity and other anthropometric and metabolic traits in 320 AP-treated FEP patients over the course of a 2-year follow-up. Methods: These patients were recruited in the multicentre PEPs study (Phenotype−genotype and environmental interaction; Application of a predictive model in first psychotic episodes). A total of 127 validated single nucleotide polymorphisms (SNPs) in 18 candidate genes were included in the genetic analysis. Results: After Bonferroni correction, SNPs in ADRA2A, FTO, CNR1, DRD2, DRD3, LEPR and BDNF were associated with obesity, abdominal circumference, triglycerides, HDL cholesterol, and/or percentage of glycated haemoglobin. Conclusions: Although our results should be interpreted as exploratory, they support previous evidence of the impact of these candidate genes on obesity and metabolic status. Further research is required to gain a better knowledge of the genetic variants that can be considered relevant metabolic risk factors. The ability to identify FEP patients at higher risk for these metabolic disturbances would enable clinicians to better select and control their AP treatment.

Download Full-text

Studies of Gene Variants Related to Inflammation, Oxidative Stress, Dyslipidemia, and Obesity: Implications for a Nutrigenetic Approach

Journal of Obesity ◽

10.1155/2011/497401 ◽

2011 ◽

Vol 2011 ◽

pp. 1-31 ◽

Cited By ~ 30

Author(s):

Maira Ladeia R. Curti ◽

Patrícia Jacob ◽

Maria Carolina Borges ◽

Marcelo Macedo Rogero ◽

Sandra Roberta G. Ferreira

Keyword(s):

Ppar Gamma ◽

Health Economy ◽

Public Health Issue ◽

Low Grade ◽

Peroxisome Proliferator ◽

Strong Impact ◽

Nucleotide Polymorphisms ◽

Metabolic Disturbances ◽

Apo E ◽

The Impact

Obesity is currently considered a serious public health issue due to its strong impact on health, economy, and quality of life. It is considered a chronic low-grade inflammation state and is directly involved in the genesis of metabolic disturbances, such as insulin resistance and dyslipidemia, which are well-known risk factors for cardiovascular disease. Furthermore, there is evidence that genetic variation that predisposes to inflammation and metabolic disturbances could interact with environmental factors, such as diet, modulating individual susceptibility to developing these conditions. This paper aims to review the possible interactions between diet and single-nucleotide polymorphisms (SNPs) in genes implicated on the inflammatory response, lipoprotein metabolism, and oxidative status. Therefore, the impact of genetic variants of the peroxisome proliferator-activated receptor-(PPAR-)gamma, tumor necrosis factor-(TNF-)alpha, interleukin (IL)-1, IL-6, apolipoprotein (Apo) A1, Apo A2, Apo A5, Apo E, glutathione peroxidases 1, 2, and 4, and selenoprotein P exposed to variations on diet composition is described.

Download Full-text

A comparison of a ketogenic diet with a LowGI/nutrigenetic diet over 6 months for weight loss and 18-month follow-up

BMC Nutrition ◽

10.1186/s40795-020-00370-7 ◽

2020 ◽

Vol 6 (1) ◽

Author(s):

Maria Vranceanu ◽

Craig Pickering ◽

Lorena Filip ◽

Ioana Ecaterina Pralea ◽

Senthil Sundaram ◽

...

Keyword(s):

Weight Loss ◽

Ketogenic Diet ◽

Dietary Intervention ◽

Hdl Cholesterol ◽

Diet Group ◽

Keto Group ◽

Nucleotide Polymorphisms ◽

Metabolic Disturbances

Abstract Background Obesity and its related metabolic disturbances represent a huge health burden on society. Many different weight loss interventions have been trialled with mixed efficacy, as demonstrated by the large number of individuals who regain weight upon completion of such interventions. There is evidence that the provision of genetic information may enhance long-term weight loss, either by increasing dietary adherence or through underlying biological mechanisms. Methods The investigators followed 114 overweight and obese subjects from a weight loss clinic in a 2-stage process. 1) A 24-week dietary intervention. The subjects self-selected whether to follow a standardized ketogenic diet (n = 53), or a personalised low-glycemic index (GI) nutrigenetic diet utilising information from 28 single nucleotide polymorphisms (n = 61). 2) After the 24-week diet period, the subjects were monitored for an additional 18 months using standard guidelines for the Keto group vs standard guidelines modified by nutrigenetic advice for the low-Glycaemic Index nutrigenetic diet (lowGI/NG) group. Results After 24 weeks, the keto group lost more weight: − 26.2 ± 3.1 kg vs − 23.5 ± 6.4 kg (p = 0.0061). However, at 18-month follow up, the subjects in the low-GI nutrigenetic diet had lost significantly more weight (− 27.5 ± 8.9 kg) than those in the ketogenic diet who had regained some weight (− 19.4 ± 5.0 kg) (p < 0.0001). Additionally, after the 24-week diet and 18-month follow up the low-GI nutrigenetic diet group had significantly greater (p < 0.0001) improvements in total cholesterol (ketogenic − 35.4 ± 32.2 mg/dl; low-GI nutrigenetic − 52.5 ± 24.3 mg/dl), HDL cholesterol (ketogenic + 4.7 ± 4.5 mg/dl; low-GI nutrigenetic + 11.9 ± 4.1 mg/dl), and fasting glucose (ketogenic − 13.7 ± 8.4 mg/dl; low-GI nutrigenetic − 24.7 ± 7.4 mg/dl). Conclusions These findings demonstrate that the ketogenic group experienced enhanced weight loss during the 24-week dietary intervention. However, at 18-month follow up, the personalised nutrition group (lowGI/NG) lost significantly more weight and experienced significantly greater improvements in measures of cholesterol and blood glucose. This suggests that personalising nutrition has the potential to enhance long-term weight loss and changes in cardiometabolic parameters. Trial registration NCT04330209, Registered 01/04/2020, retrospectively registered.

Download Full-text

Genotypes in relation to phenotypic appearance and exposure to environmental factors in Graves' hyperthyroidism

Acta Endocrinologica ◽

10.1530/eje-12-0651 ◽

2012 ◽

Vol 167 (6) ◽

pp. 783-792 ◽

Cited By ~ 8

Author(s):

Xander G Vos ◽

Erik Endert ◽

Jan G P Tijssen ◽

Wilmar M Wiersinga

Keyword(s):

Linkage Disequilibrium ◽

Environmental Factors ◽

Daily Hassles ◽

First Episode ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Specific Analysis ◽

Younger Age ◽

Caucasian Patients ◽

The Impact

BackgroundGenetic polymorphisms and environmental factors are both involved in the pathogenesis of Graves' disease, but their interaction and effect on Graves' phenotypes have scarcely been investigated.ObjectiveTo test the hypothesis that subjects with susceptibility genotypes develop more severe Graves' hyperthyroidism at a younger age and after less exposure to environmental factors, with attention to gender differences.Study designA prospective observational multicenter study in 205 adult Caucasian patients with untreated first episode of Graves' hyperthyroidism.MethodsEvaluation of genotypes (HLA DRB1*03, DQA1*05, DQB1*02; CTLA4 49A/G, CT60 A/G; PTPN22 C/T) in relation to phenotypes (age, sex, severity (clinical, biochemical, and immunological)) of hyperthyroidism and environmental factors (smoking, stress questionnaires).ResultsG-alleles in CTLA4 single nucleotide polymorphisms were dose-dependently associated with younger age at the time of diagnosis and less exposure to daily hassles. In gender-specific analysis, this association is enhanced in men and attenuated in women. Males (but not females) in HLA linkage disequilibrium had more severe (biochemical and immunological) hyperthyroidism and a tendency to younger age at diagnosis, compared with those not in linkage disequilibrium.ConclusionGraves' hyperthyroidism occurs at a younger age with less exposure to environmental factors in subjects carrying susceptibility genotypes. The impact of genotypes seems to be greater in males than in females.

Download Full-text

The role of the p53 tumor suppressor in metabolism and diabetes

Journal of Endocrinology ◽

10.1530/joe-16-0324 ◽

2016 ◽

Vol 231 (2) ◽

pp. R61-R75 ◽

Cited By ~ 48

Author(s):

Che-Pei Kung ◽

Maureen E Murphy

Keyword(s):

Tumor Suppression ◽

Metabolic Diseases ◽

Nucleotide Polymorphisms ◽

Review Of The Literature ◽

Single Nucleotide ◽

Cycle Arrest ◽

Transcription Factor P53 ◽

The Impact ◽

The Relationship

In the context of tumor suppression, p53 is an undisputedly critical protein. Functioning primarily as a transcription factor, p53 helps fend off the initiation and progression of tumors by inducing cell cycle arrest, senescence or programmed cell death (apoptosis) in cells at the earliest stages of precancerous development. Compelling evidence, however, suggests that p53 is involved in other aspects of human physiology, including metabolism. Indeed, recent studies suggest that p53 plays a significant role in the development of metabolic diseases, including diabetes, and further that p53’s role in metabolism may also be consequential to tumor suppression. Here, we present a review of the literature on the role of p53 in metabolism, diabetes, pancreatic function, glucose homeostasis and insulin resistance. Additionally, we discuss the emerging role of genetic variation in the p53 pathway (single-nucleotide polymorphisms) on the impact of p53 in metabolic disease and diabetes. A better understanding of the relationship between p53, metabolism and diabetes may one day better inform the existing and prospective therapeutic strategies to combat this rapidly growing epidemic.

Download Full-text

Increased leptin, decreased adiponectin and FGF21 concentrations in adolescent offspring of women with gestational diabetes

Acta Endocrinologica ◽

10.1530/eje-19-0658 ◽

2019 ◽

Vol 181 (6) ◽

pp. 691-700 ◽

Cited By ~ 1

Author(s):

Freja B Kampmann ◽

Anne Cathrine B Thuesen ◽

Line Hjort ◽

Anne A Bjerregaard ◽

Jorge E Chavarro ◽

...

Keyword(s):

Gestational Diabetes ◽

Metabolic Diseases ◽

Underlying Disease ◽

Independent Effect ◽

Fibroblast Growth Factor 21 ◽

Fetal Exposure ◽

Obesity Prevalence ◽

Fat Percentage ◽

Metabolic Traits ◽

The Impact

Objective Fetal exposure to gestational diabetes mellitus (GDM) increases the risk of metabolic diseases in the offspring. Leptin, adiponectin, and fibroblast growth factor 21 (FGF21) may play potential roles in the underlying disease mechanisms. We investigated the impact of fetal exposure to GDM on leptin, adiponectin, and FGF21 concentrations and their associations with measures of adiposity and metabolic traits during childhood/adolescence. Design and methods The follow-up study included 504 GDM and 540 control offspring aged 9–16 from the Danish National Birth Cohort. Anthropometric measurements, fasting blood samples, puberty status and fat percentages by dual-energy X-ray absorptiometry were examined. Serum concentrations of leptin, adiponectin, and FGF21 were measured by validated immune assays. Results GDM offspring had 38% (95% CI: 22–55%) higher leptin, 0.6 mg/L (95% CI: −1.2, −0.04 mg/L) lower adiponectin, and 32% (95% CI: −47%, −12%) lower FGF21 concentrations than control offspring (P < 0.05). After adjustment for confounders including maternal pre-pregnancy BMI, GDM offspring had borderline higher leptin (P = 0.06) and significantly lower FGF21 concentrations (P = 0.006). When accounting for offspring BMI z-score, GDM exposure had no significant independent effect on leptin or adiponectin concentrations, whereas FGF21 was still significant. In univariate analyses, leptin and adiponectin were associated with fasting insulin, HOMA-IR, and adiposity, and FGF21 with total fat percentage. Conclusions GDM offspring had higher leptin, lower adiponectin and FGF21 concentrations than control offspring. Elevated leptin and decreased adiponectin concentrations associated with adverse metabolic traits and were most likely driven by higher obesity prevalence among GDM offspring. The functional implications of decreased FGF21 concentrations among GDM offspring need to be further explored.

Download Full-text

THERAPY OF ENDOCRINE DISEASE: Testosterone supplementation and body composition: results from a meta-analysis study

Acta Endocrinologica ◽

10.1530/eje-15-0262 ◽

2016 ◽

Vol 174 (3) ◽

pp. R99-R116 ◽

Cited By ~ 106

Author(s):

Giovanni Corona ◽

Vito A Giagulli ◽

Elisa Maseroli ◽

Linda Vignozzi ◽

Antonio Aversa ◽

...

Keyword(s):

Body Composition ◽

Metabolic Diseases ◽

Meta Analysis ◽

Hdl Cholesterol ◽

Metabolic Disturbances ◽

Cholesterol Levels ◽

Metabolic Outcomes ◽

Improve Body Composition ◽

Fasting Glycaemia ◽

And Control

ObjectiveThe role of testosterone (T) in regulating body composition is conflicting. Thus, our goal is to meta-analyse the effects of T supplementation (TS) on body composition and metabolic outcomes.MethodsAll randomized controlled trials (RCTs) comparing the effect of TS on different endpoints were considered.ResultsOverall, 59 trials were included in the study enrolling 3029 and 2049 patients in TS and control groups respectively. TS was associated with any significant modification in body weight, waist circumference and BMI. Conversely, TS was associated with a significant reduction in fat and with an increase in lean mass as well as with a reduction of fasting glycaemia and insulin resistance. The effect on fasting glycaemia was even higher in younger individuals and in those with metabolic diseases. When only RCTs enrolling hypogonadal (total T <12 mol/l) subjects were considered, a reduction of total cholesterol as well as triglyceride (TGs) levels were also detected. Conversely, an improvement in HDL cholesterol levels as well as in both systolic and diastolic blood pressure was not observed.ConclusionOur data suggest that TS is able to improve body composition and glycometabolic profile particularly in younger subjects and in those with metabolic disturbances. Specifically designed studies are urgently needed to confirm this point.

Download Full-text

Adipose Morphology: a Critical Factor in Regulation of Human Metabolic Diseases and Adipose Tissue Dysfunction

Obesity Surgery ◽

10.1007/s11695-020-04983-6 ◽

2020 ◽

Vol 30 (12) ◽

pp. 5086-5100 ◽

Cited By ~ 1

Author(s):

Fangcen Liu ◽

Jielei He ◽

Hongdong Wang ◽

Dalong Zhu ◽

Yan Bi

Keyword(s):

Adipose Tissue ◽

Metabolic Diseases ◽

Critical Role ◽

Critical Factor ◽

Critical Event ◽

Metabolic Disturbances ◽

Metabolic Dysregulation ◽

Adipocyte Hypertrophy ◽

Adipose Dysfunction ◽

The Impact

AbstractEmerging evidence highlights that dysfunction of adipose tissue contributes to impaired insulin sensitivity and systemic metabolic deterioration in obese state. Of note, adipocyte hypertrophy serves as a critical event which associates closely with adipose dysfunction. An increase in cell size exacerbates hypoxia and inflammation as well as excessive collagen deposition, finally leading to metabolic dysregulation. Specific mechanisms of adipocyte hypertrophy include dysregulated differentiation and maturation of preadipocytes, enlargement of lipid droplets, and abnormal adipocyte osmolarity sensors. Also, weight loss therapies exert profound influence on adipocyte size. Here, we summarize the critical role of adipocyte hypertrophy in the development of metabolic disturbances. Future studies are required to establish a standard criterion of size measurement to better clarify the impact of adipocyte hypertrophy on changes in metabolic homeostasis.

Download Full-text

Physical and nutritional activity as an intervention against obesity

GSC Advanced Research and Reviews ◽

10.30574/gscarr.2021.9.3.0282 ◽

2021 ◽

Vol 9 (3) ◽

pp. 013-020

Author(s):

Guillermina Arenas Montaño ◽

Ramírez Cortes Ariel

Keyword(s):

Physical Activity ◽

Body Fat ◽

Metabolic Diseases ◽

Statistical Significance ◽

Clinical History ◽

Overweight And Obesity ◽

Abdominal Circumference ◽

Obese Women ◽

Obesity And Overweight ◽

The Impact

Introduction: Obesity and overweight are the most dominant chronic non-communicable pathologies of the century, causing metabolic diseases, such as Diabetes Mellitus and Arterial Hypertension. With WHO data indicating that since 1980 it has more than doubled worldwide, in 2008 1.5 billion adults were overweight, of this number 200 million men were obese and 300 million were obese women. Such is the impact that the WHO declared obesity and overweight as a worldwide epidemic. Objective: To identify the integral health status of university students by means of a clinical history, healthy and unhealthy lifestyles related to nutrition and physical activity. Method: We studied a population of 50 students, 19 males and 31 females, of different degrees of the Facultad de Estudios Superiores Iztacala, with overweight and obesity, and interested in improving their eating habits and lifestyles and are attended in the clinics of the disease prevention program (PROSALUD). Results: There was a statistical reduction in the average BMI and abdominal circumference, but no decrease in the percentage of body fat. Conclusions: Constancy in physical activity is a vital constant in weight reduction, along with diet, however described this in the literature that more time is required with this discipline to obtain statistical significance in the reduction of body fat, it is highly recommended the intervention plan used in the PROSALUD program to attend students with overweight and metabolic problems

Download Full-text

Thrombophilia and risk of VTE recurrence according to the age at the time of first VTE manifestation

VASA ◽

10.1024/0301-1526/a000447 ◽

2015 ◽

Vol 44 (4) ◽

pp. 313-323 ◽

Cited By ~ 6

Author(s):

Lea Weingarz ◽

Marc Schindewolf ◽

Jan Schwonberg ◽

Carola Hecking ◽

Zsuzsanna Wolf ◽

...

Keyword(s):

Factor V Leiden ◽

Cox Proportional Hazards ◽

First Episode ◽

Factor V ◽

Factor V Leiden Mutation ◽

Younger Patients ◽

Risk Of Recurrence ◽

G20210a Mutation ◽

Increased Risk ◽

The Impact

Abstract. Background: Whether screening for thrombophilia is useful for patients after a first episode of venous thromboembolism (VTE) is a controversial issue. However, the impact of thrombophilia on the risk of recurrence may vary depending on the patient’s age at the time of the first VTE. Patients and methods: Of 1221 VTE patients (42 % males) registered in the MAISTHRO (MAin-ISar-THROmbosis) registry, 261 experienced VTE recurrence during a 5-year follow-up after the discontinuation of anticoagulant therapy. Results: Thrombophilia was more common among patients with VTE recurrence than those without (58.6 % vs. 50.3 %; p = 0.017). Stratifying patients by the age at the time of their initial VTE, Cox proportional hazards analyses adjusted for age, sex and the presence or absence of established risk factors revealed a heterozygous prothrombin (PT) G20210A mutation (hazard ratio (HR) 2.65; 95 %-confidence interval (CI) 1.71 - 4.12; p < 0.001), homozygosity/double heterozygosity for the factor V Leiden and/or PT mutation (HR 2.35; 95 %-CI 1.09 - 5.07, p = 0.030), and an antithrombin deficiency (HR 2.12; 95 %-CI 1.12 - 4.10; p = 0.021) to predict recurrent VTE in patients aged 40 years or older, whereas lupus anticoagulants (HR 3.05; 95%-CI 1.40 - 6.66; p = 0.005) increased the risk of recurrence in younger patients. Subgroup analyses revealed an increased risk of recurrence for a heterozygous factor V Leiden mutation only in young females without hormonal treatment whereas the predictive value of a heterozygous PT mutation was restricted to males over the age of 40 years. Conclusions: Our data do not support a preference of younger patients for thrombophilia testing after a first venous thromboembolic event.

Download Full-text