Genetic variations in regulatory pathways of fatty acid and glucose metabolism are associated with obesity phenotypes: a population-based cohort study

Berg, Sophie; Dollé, Martijn E.T.; Imholz, Sandra; Slot, Ruben van ‘t; Wijmenga, Cisca; Verschuren, W M Monique; Strien, C.; Siezen, Christine L. E.; Hoebee, Barbara; Feskens, Edith J. M.; Boer, Jolanda M. A.

doi:10.1038/ijo.2009.152

Cited by 51 publications

(30 citation statements)

References 57 publications

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“…The present study selected subjects from the ongoing Doetinchem cohort (Lu et al 2008;van den Berg et al 2009). The design of the Doetinchem study and detailed methods have been reported earlier (Verschuren et al 2008).…”

Section: Study Populationmentioning

confidence: 99%

“…At the start of the study, a blood sample was drawn, fractionated to obtain buffy coats for isolation of DNA and subsequently stored at -30°C. DNA isolation, SNP selection and genotyping Genomic DNA was isolated from stored buffy coats using a salting out method as described before (van den Berg et al 2009). To ensure a considerable fraction of carriers of the minor allele, only SNPs with a minor allele frequency in Europeans of at least 25 %, as indicated in the SNP public database (dbSNP; http://www.ncbi.nlm.nih.gov/SNP), were considered as candidates.…”

Section: Study Populationmentioning

confidence: 99%

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

et al. 2014

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Weight gain, when it leads to overweight or obesity, is nowadays one of the major health problems. ACE, FTO, AKR1C2, TIMP4 and MMP2 genes have been implicated in previous studies on weight regulation. This study investigated the contribution of polymorphisms in these five candidate genes to the risk of weight gain over a 10-year time period. Two groups were selected from participants of the Doetinchem cohort study who were followed over a 10-year period: A stable weight group (±2 kg/10 year; n = 259) and a weight gainers group who increased their body weight by roughly 10 % ([8 kg/ 10 year; n = 237). Starting BMI was between 20 and 35 kg/m 2 and baseline age between 20 and 45 years. Selected SNPs and insert/deletion in candidate genes were measured in each group. In men, the allelic distribution of FTO rs9939609 (v 2 p = 0.005), ACE rs4340 (v 2 p = 0.006) and AKR1C2 rs12249281 (v 2 p = 0.019) differed between the weight stable and weight gainers group. Interaction between FTO rs9939609 and ACE rs4340 was observed. In women, the allelic distribution of MMP2 rs1132896 differed between the weight stable and weight gainers group (v 2 p = 0.00001). The A-allele of FTO was associated with a 1.999 higher risk of gaining weight in men (OR 1.99, p = 0.020), while in women, the C-allele of MMP2 was associated with a 2.509 higher risk of weight gain (OR 2.50, p = 0.001) over the 10-year period. We found that FTO in men and MMP2 in women are associated with weight gain over a 10-year follow-up period.

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Section: Study Populationmentioning

confidence: 99%

Section: Study Populationmentioning

confidence: 99%

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

et al. 2014

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“…Inclusion criteria for genetic studies were stable smoking behavior and absence of pregnancy at time of measurement as described previously. 9 Data from four visit rounds are now available. However, waist circumference was not assessed in the first measurement round.…”

Section: Study Populationsmentioning

confidence: 99%

Codon 72 polymorphism (rs1042522) of TP53 is associated with changes in diastolic blood pressure over time

et al. 2011

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p53 is involved in stress response, metabolism and cardiovascular functioning. The C-allele of rs1042522 in the gene encoding for p53 is associated with longevity and cancer. In this study, we aimed to investigate the association of rs1042522 with changes in blood pressure, BMI and waist circumference using a longitudinal approach. Rs1042522 was analyzed in two longitudinal studies; the Doetinchem Cohort Study (DCS) and the Botnia Prospective Study (BPS). Changes in quantitative traits over time were investigated according to rs1042522 genotypes. An association between rs1042522 and changes in diastolic blood pressure (DBP) in the DCS over time was observed (P¼0.004). Furthermore, a borderline significant association was detected with changes in waist circumference over time (P¼0.03). These findings were also observed in the BPS (P¼0.02 and P¼0.05). The C/C-genotype (Pro/Pro) showed the most moderate time-related increase for the studied endpoints. Furthermore, data from the BPS suggested that the C/C-genotype protects against increases in glucose levels over time at 30 and 60 min during oral glucose tolerance test (P¼0.01 and P¼0.02). In conclusion, we found an association between the C/C-genotype of rs1042522 and changes in DBP and waist circumference over time. This might contribute to the longevity phenotype observed for the same genotype by others.

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“…All yielded the same results, except for two SNPs, which were, therefore, excluded. 16 Thus, data on 353 SNPs in 239 genes were available for 3244 participants.…”

Section: Genotypingmentioning

confidence: 99%

Glucose levels and genetic variants across transcriptional pathways: interaction effects with BMI

et al. 2010

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Objective: Much of the genetic variation in glucose levels remains to be discovered. Especially, research on gene-environment interactions is scarce. Overweight is one of the main risk factors for hyperglycemia. As transcriptional regulation is important for both weight maintenance and glucose control, we analyzed 353 single nucleotide polymorphisms (SNPs), occurring in transcriptional pathways of glucose and lipid metabolism in interaction with body mass index (BMI) on glucose levels. Research design and methods: SNPs were measured in 3244 participants of the Doetichem cohort. Non-fasting glucose levels and BMI were measured twice in 6 years. SNP Â BMI interactions were analyzed by mixed models and adjusted for age, sex, time since last meal, and follow-up time. False discovery rate (FDR) o0.2 was used to adjust for multiple testing. Results: Two SNPs in the PPARGC1A gene (rs8192678, FDR ¼ 0.07; rs3755863, FDR ¼ 0.17) showed a significant interaction with BMI. The rare allele of both SNPs was associated with significantly lower glucose levels in subjects with a BMIp25 kg m -2 (rs8192678, P ¼ 0.02; rs3755863, P ¼ 0.03). An inverse association was suggested in subjects with a BMI428 kg m -2 . A small intervention study (n ¼ 120) showed similar, though non-significant, results. Conclusions: Using a pathway-based approach, we found that BMI significantly modified the association between two SNPs in the PPARGC1A gene and glucose levels. The association between glucose and PPARGC1A was only present in lean subjects. This suggests that the effect of the PPARGC1A gene, which is involved both in fatty acid oxidation and glucose metabolism, is modified by BMI.

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Genetic variations in regulatory pathways of fatty acid and glucose metabolism are associated with obesity phenotypes: a population-based cohort study

Cited by 51 publications

References 57 publications

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

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

Codon 72 polymorphism (rs1042522) of TP53 is associated with changes in diastolic blood pressure over time

Glucose levels and genetic variants across transcriptional pathways: interaction effects with BMI

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