Gender-specific genetic associations of polymorphisms in ACE, AKR1C2, FTO and MMP2 with weight gain over a 10-year period

Bouwman, Freek G.; Boer, Jolanda M. A.; Imholz, Sandra; Wang, Ping; Dollé, Martijn E.T.; Mariman, E.C.M.

doi:10.1007/s12263-014-0434-2

Cited by 16 publications

(12 citation statements)

References 63 publications

(70 reference statements)

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“…The genotyping of the FTO rs9939609 polymorphism [intronic nucleotide substitution T>A; reported global minor allele frequency 0.34, http://www.ncbi.nlm.nih.gov/projects/SNP] was carried out using real‐time PCR with TaqMan SNP Genotyping Assays from Applied Biosystems (Foster City, CA) at the Tufts University in Boston. The minor allele frequency in our cohort was 0.38, which is in accordance with various European populations reported previously . Genotyping success rate for the entire cohort was 99.1%.…”

Section: Methodssupporting

confidence: 91%

Association of the fat mass and obesity‐associated gene risk allele, rs9939609A, and reward‐related brain structures

Groot

Felius

Trompet

et al. 2015

Obesity

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Objective: Recently, the fat mass and obesity-associated gene (FTO) has been identified as a genetic risk factor for developing obesity. The underlying mechanisms remain speculative. SNPs within FTO have been associated with brain atrophy in frontal and occipital regions, suggesting that FTO might affect body weight through cerebral pathways. Behavioral studies suggested a relationship between FTO and the reward-related behavioral traits. Therefore the relationship between the FTO risk allele rs9939609A and volumes of reward-related brain structures has been investigated. Methods: Four hundred and ninety-two Dutch individuals (56% males, age: 70-82 years) participating in the PROSPER study underwent a 3D-T1-weighted MRI to assess the volumes of reward-related brain structures (e.g., amygdala, nucleus accumbens) and of gray matter and white matter. Linear regression analysis was performed to test for the association of subcortical and cortical structures with rs9939609A. Results: rs9939609A is associated with lower volumes of the nucleus accumbens (p=0.03) and trended toward lower cortical gray matter volumes (p=0.08). This association is independent of gender, age, and BMI, FDR corrected. Conclusions: The FTO risk allele is associated with lower nucleus accumbens volumes, suggesting that the higher body weight of risk-allele carriers might be due to changes within reward-related brain structures.

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Section: Methodssupporting

confidence: 91%

Association of the fat mass and obesity‐associated gene risk allele, rs9939609A, and reward‐related brain structures

Groot

Felius

Trompet

et al. 2015

Obesity

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“…The results from our study indicate that MMP2 rs1132896 (C/C genotype) is a predictor for high weight loss at 3 months. In a recent study on long-term weight development, the C-allele was found to be associated with risk for weight gain in women [33] . In a study among Koreans, the C-allele of MMP2 rs1132896 was found to increase the risk for the development of obesity [34] .…”

Section: Discussionmentioning

confidence: 96%

Genetic Predictors of ≥5% Weight Loss by Multidisciplinary Advice to Severely Obese Subjects

Aller¹,

Mariman²,

Bouwman³

et al. 2017

Lifestyle Genomics

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Background:Weight loss success is determined by genetic factors, which may differ according to treatment strategy. Methods: From a multidisciplinary obesity treatment program involving dietary advice, psychological counseling, and increased physical activity, 587 subjects (68% female; 46.1 ± 12.4 years; BMI 39.9 ± 6.3) were recruited. At baseline, a blood sample was drawn for DNA isolation. Genotypes were determined for 30 polymorphisms in 25 candidate genes. The association between genotypes and weight loss was assessed after 3 months (short-term) and after 12 months of treatment (long-term). Weight loss was categorized as ≥ 5% or <5% of initial weight. Results: The G/G genotype of PLIN1 (rs2289487) and PLIN1 (rs2304795), the T/T genotype of PLIN1 (rs1052700), and the C/C genotype of MMP2 predicted ≥ 5% weight loss in the first 3 months. The C/G-G/G genotype of PPARγ (rs1801282) and the T/C genotype of TIMP4 (rs3755724) predicted ≥ 5% weight loss after 12 months. Subjects with the combination of PPARγ (rs1801282) C/G-G/G and TIMP4 (rs3755724) T/C lost even more weight. Conclusion: Polymorphisms in genes related to regulation of fat storage and structural adaptation of the adipocytes are predictors for weight loss success with different genes being relevant for short-term and long-term weight loss success.

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“…; Bouwman et al. ). Furthermore, higher levels of the product of ACE, angiotensin II (Ang II), stimulates adipocyte differentiation (Frigolet et al.…”

Section: Discussionmentioning

confidence: 97%

“…However, more mechanistic studies are needed to confirm this hypothesis. ACE has been implicated in obesity because ACE polymorphisms were associated with body weight and obesity incidence (Lagou et al 2007;Bouwman et al 2014). Furthermore, higher levels of the product of ACE, angiotensin II (Ang II), stimulates adipocyte differentiation (Frigolet et al 2013) and could thereby affect adipose tissue mass.…”

Section: Discussionmentioning

confidence: 99%

Dietary weight loss‐induced changes in RBP4, FFA, and ACE predict weight regain in people with overweight and obesity

Vink

Roumans

Mariman

et al. 2017

Physiological Reports

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Adipokines and other biomarkers were previously identified with roles in energy expenditure, appetite, satiety, and adiposity. Therefore, we investigated whether dietary weight loss‐induced changes in adipokines and other biomarkers known to play a role in weight regulation or energy expenditure could predict weight regain in people with overweight and obesity. In this randomized controlled trial 26 males and 30 females (BMI: 28–35 kg/m2) followed either a low‐calorie diet (LCD; 1250 kcal/day) for 12 weeks or a very‐low‐calorie diet (VLCD; 500 kcal/day) for 5 weeks followed by a weight stable period of 4 weeks (dietary intervention (DI) period) and a 9‐month follow‐up period. Blood samples were taken before and after each period to measure FFA, TAG, total cholesterol, insulin, glucose, angiotensin‐converting enzyme (ACE) activity, IL‐6, RBP4, apelin, leptin, adiponectin, vaspin, and nesfatin‐1 concentrations. Weight loss was similar between groups (LCD: −8.2 ± 0.5 kg; VLCD: −8.9 ± 0.4 kg, P = 0.30). Only changes in ACE activity, FFA and RBP4 concentrations during DI were correlated with weight regain in the whole group (r = −0.299, P = 0.030, r = −0.274, P = 0.047, and r = 0.357, P = 0.008, respectively). Together they explained 28% (r = 0.532) of weight regain variation. Dietary weight loss‐induced changes in ACE activity, FFA and RBP4 independently contribute to weight regain prediction.

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Gender-specific genetic associations of polymorphisms in ACE, AKR1C2, FTO and MMP2 with weight gain over a 10-year period

Cited by 16 publications

References 63 publications

Association of the fat mass and obesity‐associated gene risk allele, rs9939609A, and reward‐related brain structures

Association of the fat mass and obesity‐associated gene risk allele, rs9939609A, and reward‐related brain structures

Genetic Predictors of ≥5% Weight Loss by Multidisciplinary Advice to Severely Obese Subjects

Dietary weight loss‐induced changes in RBP4, FFA, and ACE predict weight regain in people with overweight and obesity

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