The A-allele of the common FTO gene variant rs9939609 complicates weight maintenance in severe obese patients

Woehning, Annika; Schultz, Jobst‐Hendrik; Roeder, Eva; Moeltner, Andreas; Isermann, Berend; Nawroth, PP; Wolfrum, Christian; Rudofsky, Gottfried

doi:10.1038/ijo.2012.14

Cited by 30 publications

(27 citation statements)

References 26 publications

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“…A detailed screening flow is shown in Figure 1. Of the 14 selected articles, 10 reported the results of an additive genetic model (TA compared with TT, AA compared with TT) (6,7,11,12,(16)(17)(18)(19)(20)(21), whereas the other 4 articles reported the results of a dominant genetic model (TA/AA compared with TT) (13,15,25,26), which was mainly the result of limited sample size in these 4 studies. Given the known additive genetic effect of FTO variant on BMI and obesity risk, our primary analyses focused on the 10 studies that reported additive genetic model results.…”

Section: Results Of Literature Searchmentioning

confidence: 89%

“…One study explicitly mentioned that the model was unadjusted (25). For the other 4 studies (13,15,16,18), no information was provided regarding the statistical adjustment.…”

Section: Study Characteristicsmentioning

confidence: 99%

“…One study presented the results (mean weight changes) in a figure (24), and we extracted the estimates carefully from the given figure. For studies with an initial weightloss phase followed by a weight-maintenance phase (16,17,24), we used data on long-term weight loss. For studies that reported results of weight change without exactable data (14,28,29), we contacted the first or corresponding authors to request detailed data; 2 authors replied with the requested data (14,28).…”

Section: Data Extractionmentioning

confidence: 99%

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FTO genotype and weight loss in diet and lifestyle interventions: a systematic review and meta-analysis

Xiang

Pan

et al. 2016

The American Journal of Clinical Nutrition

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Background: Studies have suggested that the fat mass and obesityassociated (FTO) genotype is associated with individual variability in weight loss in response to diet/lifestyle interventions, but results are inconsistent. Objective: We aimed to provide a summary of the literature evaluating the relation between the FTO genotype and weight loss in response to diet/lifestyle interventions. Design: A search of English-language articles in the PubMed and Embase databases (through 30 April 2015) was performed. Eligible studies were diet/lifestyle weight-loss intervention studies conducted in adults that reported changes in body weight or body mass index (BMI) by the FTO variant rs9939609 (or its proxy). Differences in weight loss between FTO genotypes across studies were pooled with the use of fixed-effect models. Results: A meta-analysis of 10 studies (comprising 6951 participants) that reported the results of additive genetic models showed that individuals with the FTO TA genotype and AA genotype (those with the obesity-predisposing A allele) had 0.18-kg (95% CI: 20.09-, 0.45-kg; P = 0.19; NS) and 0.44-kg (95% CI: 0.09-, 0.79-kg; P = 0.015) greater weight loss, respectively, than those with the TT genotype. A metaanalysis of 14 studies (comprising 7700 participants) that reported the results of dominant genetic models indicated a 0.20-kg (20.43-, 0.04-kg) greater weight loss in the TA/AA genotype than in the TT genotype (P = 0.10). In addition, differences in weight loss between the AA genotype and TT genotype were significant in studies with a diet intervention only, adjustment for baseline BMI or body weight, and several other subgroups. However, the relatively small number of studies limited these stratified analyses, and there was no statistically significant difference between subgroups. Conclusions: This meta-analysis suggests that individuals carrying the homozygous FTO obesity-predisposing allele may lose more weight through diet/lifestyle interventions than noncarriers. Our data provide evidence for genetic variability in response to diet/lifestyle interventions on weight loss, although clinical applications of these findings need further investigations.

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Section: Results Of Literature Searchmentioning

confidence: 89%

“…One study explicitly mentioned that the model was unadjusted (25). For the other 4 studies (13,15,16,18), no information was provided regarding the statistical adjustment.…”

Section: Study Characteristicsmentioning

confidence: 99%

Section: Data Extractionmentioning

confidence: 99%

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FTO genotype and weight loss in diet and lifestyle interventions: a systematic review and meta-analysis

Xiang

Pan

et al. 2016

The American Journal of Clinical Nutrition

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“…Interestingly, it has been shown that physical inactivity was associated with a BMI increase (1.95 ± 0.3 kg/m 2 ) in homozygous A-allele carriers compared with homozygous T-allele carriers (Andreasen et al 2008). The FTO genotype has also been shown to interact with weight loss (Delahanty et al 2012), and the A-allele seems to complicate weight maintenance in severe obese patients (Woehning et al 2013). Studies also show that the A-allele is associated with increased energy intake (Speakman et al 2008), but this could not be confirmed in the present study.…”

Section: Discussionmentioning

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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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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“…Individual lifestyle factors, such as eating habits or physical activity, are major contributors to the development of obesity (Ogden et al 2007). However, various genetic and neurobiological factors are also acknowledged to impact on the pathogenesis of obesity Need et al 2006;Bray 2006;Rankinen et al 2006;Winkler et al 2012;Woehning et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Genetic modulation of the serotonergic pathway: influence on weight reduction and weight maintenance

et al. 2013

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The serotonergic pathway plays a major role in the development of obesity. Its activity can be modulated by the 5-HT transporter-linked polymorphic region in the SLC6A4 gene and the upstream variable number of tandem repeats polymorphism in the MAOA gene. We studied whether these genetic modulations have an influence on weight reduction and weight maintenance in a one-year weight reduction program (OPTIFAST Ò 52). The polymorphisms were genotyped by PCR in a sample of 135 female and 67 male subjects with severe obesity (44 ± 13 years, 122.3 ± 22.2 kg, BMI: 41.7 ± 6.7 kg/m 2 ). The program leads to a total weight loss of 19.9 ± 9.8 kg (16.9 ± 8.3 %) in women and 27.4 ± 13.6 kg (20.4 ± 9.9 %) in men. Anthropometric measurements and blood levels were determined at the start of the program (T0), after the weight reduction phase (T1) and after the subsequent weight maintenance phase at the end of the program (T2). Each polymorphism alone did not significantly influence weight loss or weight maintenance neither in men nor in women. However, women carrying both risk genotypes (SS and 3/3) displayed a lower total weight loss during the program (p = 0.05). This effect derived mainly from difficulties in the weight maintenance phase (p = 0.11), while the weight reduction phase was not affected (p = 0.61). No influence was found in men (p = 0.93). Modulation of the serotonergic pathway by carrying both risk alleles seems to influence success of weight loss programs in women with severe obesity due to problems in stabilizing body weight after weight reduction.

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The A-allele of the common FTO gene variant rs9939609 complicates weight maintenance in severe obese patients

Abstract: In this program, the AA-genotype of rs9939609 was associated with a higher initial body weight and did influence success of weight stabilization. Thus, emphasizing the maintenance phase during a weight reduction program might result in better success for AA-genotype carriers.

Cited by 30 publications

References 26 publications

FTO genotype and weight loss in diet and lifestyle interventions: a systematic review and meta-analysis

FTO genotype and weight loss in diet and lifestyle interventions: a systematic review and meta-analysis

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

Genetic modulation of the serotonergic pathway: influence on weight reduction and weight maintenance

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