β3-adrenergic-receptor allele distributions in children, adolescents and young adults with obesity, underweight or anorexia nervosa

Hinney, Anke; Lentes, K.-U.; Rosenkranz, K.; Barth, Nikolaus; Roth, Helmut; Ziegler, Andreas; Hennighausen, Klaus; Coners, H; Wurmser, Harald; Jacob, Kathryn J; Romer, G. Schenk; Winnikes, Ulrike; Mayer, Hermann; Herzog, Wolfgang; Lehmkuhl, Gerd; Poustka, Fritz; Mh, Schmidt; Blum, WF; Pirke, Karl‐Martin; Schäfer, Helmut; Kh, Grzeschik; Remschmidt, Helmut; Hebebrand, Johannes

doi:10.1038/sj.ijo.0800391

Cited by 78 publications

(49 citation statements)

References 18 publications

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“…These results are consistent with those of the main meta-analysis. From the weighted regression analysis, neither the linear nor the quadratic effect of the 3,8,11,12,21); N: non-diabetics (ID; 2,5,7,13,14,19,20,22,23,26,30,31); CaU: combinedaUnknown (ID; 1,4,6,9,10,15,16,17,18,24,25,27,28,29,32,33,34,35,36).…”

Section: Sensitivity Analysismentioning

confidence: 99%

Meta-analysis of the association of the Trp64Arg polymorphism in the β3 adrenergic receptor with body mass index

et al. 1998

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OBJECTIVE: As a result of efforts to isolate obesity-promoting genes, the Trp64Arg polymorphism in the b b 3 adrenergic receptor locus, has been studied by many investigators. Results of the studies have varied in statistical signi®cance and magnitude of the association of the polymorphism with body mass index (BMI: kgam 2 ). This has led to controversy about whether this polymorphism is associated with meaningful changes in BMI. To clarify the possible association, we conducted a meta-analysis. DESIGN: Meta-analytic study. MEASUREMENTS: For each genotype of the b b 3 adrenergic receptor (TrpaTrp; TrpaArg; ArgaArg), we extracted the number of subjects, mean and standard deviation of BMI from 23 studies, including 36 different subgroups with a total of 7399 subjects. Other indices and obesity-related variables were not considered. RESULTS: No signi®cant association of the Trp64Arg polymorphism with BMI was found. The weighted mean BMI difference beween TrpaTrp homozygotes and TrpaArg heterozygotes was 0.19 (s.e. 0.11; P 0.07). In addition, the distribution of effect sizes was not signi®cantly heterogeneous (w w 2 38.68; df 35; P 0.31) suggesting that the variation of the effect sizes across the subgroups is not signi®cant. A further weighted regression analysis, utilizing all three genotypes and adjusting for the random subgroup effect, also showed the effect of the polymorphism on BMI is not signi®cant (F 1.72, df (2,54), P 0.19). CONCLUSION: Based on existing data, the Trp64Arg polymorphism does not appear to be signi®cantly associated with BMI. Moreover, we found no evidence for effect heterogeneity, suggesting that the effect of the polymorphism is not moderated by ethnicity or diabetic status.

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Section: Sensitivity Analysismentioning

confidence: 99%

Meta-analysis of the association of the Trp64Arg polymorphism in the β3 adrenergic receptor with body mass index

et al. 1998

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“…3,4 Their allelic frequencies range from 0.08 to 0.25 for the polymorphism Pro12Ala of the PPARg2 gene and from 0.05 to 0.19 for Trp64Arg variant of the ADRb3 gene in Caucasian populations. [5][6][7][8][9][10] Interestingly, Hsueh et al 11 found a gene Â gene interaction on obesity between variants of ADRb3 (Trp64Arg) and PPARg2 (Pro12Ala) in Mexican-American adults. They reported that these two polymorphisms accounted for 2-3% of the total variation in BMI, serum insulin and leptin, with the interaction accounting for about half of their total effect.…”

Section: Introductionmentioning

confidence: 99%

Gene–gene interaction between PPARγ2 and ADRβ3 increases obesity risk in children and adolescents

et al. 2004

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AIMS:Multiple genes are likely to be involved in obesity and these genes may interact with environmental factors to influence obesity risk. Our aim was to explore the synergistic contribution of the two polymorphisms: Pro12Ala of the PPARg2 gene and Trp64Arg of the ADRb3 gene to obesity risk in a Spanish children and adolescent population. METHODS: We designed a sex-and age-matched case-control study. Participants were 185 obese and 185 control children (aged 5-18 y) from the Navarra region, recruited through Departments of Pediatrics (Hospital Virgen del Camino, Navarra University Clinic and several Primary Health Centers). The obesity criterion (case definition) was BMI above the 97th percentile according to Spanish BMI reference data for age and gender. Anthropometric parameters were measured by standard protocols. The genotype was assessed by PCR-RFLP after digestion with BstUI for PPARg2 mutation and BstNI for ADRb3 variants. Face-toface interviews were conducted to assess the physical activity. Using a validated physical activity questionnaire, we computed an activity metabolic equivalent index (METs h/week), which represents the physical exercise during the week for each participant. Statistical analysis was performed by conditional logistic regression, taking into account the matching between cases and controls. RESULTS: Carriers of the polymorphism Pro12Ala of the PPARg2 gene had a significantly higher obesity risk than noncarriers (odds ratio (OR) ¼ 2.18, 95% CI ¼ 1.09-4.36) when we adjusted for sex, age and physical activity. Moreover, the risk of obesity was higher (OR ¼ 2.59, 95% CI ¼ 1.17-5.34) when family history of obesity was also taken into account in the model. The OR for obesity linked to both polymorphisms (PPARg2 and ADRb3) was 5.30 (95% CI ¼ 1.08-25.97) when we adjusted for sex, age and physical activity. After adjustment for family history of obesity, the OR for carriers of both polymorphisms was 19.5 (95% CI ¼ 2.43-146.8). CONCLUSIONS: A synergistic effect between polymorphism Pro12Ala of the PPARg2 gene and Trp64Arg of the ADRb3 gene for obesity risk was found in a case-control study including children and adolescents.

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“…Data from Germany have failed to show association with a number of candidate loci. [1][2][3] However, the list of genes that might theoretically play a role in this disorder is far from exhausted.…”

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confidence: 99%

Association between a marker in the UCP-2/UCP-3 gene cluster and genetic susceptibility to anorexia nervosa

et al. 1999

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Anorexia nervosa (AN) is an enigmatic syndrome affecting approximately 0.1% of the at risk population in the UK which equates to approximately 70 000 sufferers. Data from a number of studies have demonstrated the heritability of this disorder, however it is only in the last few years that studies have begun to determine the involvement of particular candidate genes in this genetic predisposition. In the current study we have used classical case-control association analysis to determine whether two highly polymorphic microsatellite markers, located within a 3-cM region of the UCP-2/UCP-3 locus, show involvement of this region of the human genome in the predisposition to AN. Analysis of a cohort of 170 female Caucasian anorexia nervosa sufferers and 150 normal female controls shows evidence of association with the marker D11S911 but not D11S916. Allele 13 of the marker D11S911 is significantly over represented in the anorexia nervosa population suggesting that a mutation in linkage disequilibrium with this locus may form part of the genetic component of AN. Further work is now required to try to reproduce these data in a second independent cohort and to further characterise this region of the human genome.Recently, there has been an upsurge of interest in the genetics of anorexia nervosa (AN). There is now more acceptance that this disorder, once thought of purely in psycho-social terms, has a sizeable genetic component. Data from Germany have failed to show association with a number of candidate loci. 1-3 However, the list of genes that might theoretically play a role in this disorder is far from exhausted.It has been suggested that AN may involve an aberration in the serotonergic system. Recent data from Collier and colleagues 4 demonstrate a putative association between a polymorphism in the promoter region of the 5-HTR 2A gene and genetic predisposition to AN. However, we 5 and others 1 have been unable to confirm this initial observation. The debate regarding the involvement of this locus in the genetic predisposition to AN is still unclear and two further small studies also claim association at this locus. 6,7 In the current study we focused on two further candidates, namely UCP-2 and UCP-3. The protein products of these genes are ubiquitously expressed and are thought to have a role in the control of energy expenditure and metabolic adaptation during fasting. 8 Several studies, including that of Moukaddem and colleagues, 9 describe the difficulty of inducing weight gain in AN patients, and that unusually high energy intakes are required to maintain a normal weight after refeeding. Indeed, these patients seem to maintain a low body mass with relative ease. Given the involvement of UCP-2 and UCP-3 in thermogenesis, the two corresponding genes are plausible candidates for a role in the genetic susceptibility to AN.The genes for UCP-2 and UCP-3 co-localise to a 10.5 cR 3000 , or ෂ3-cM, region of human chromosome 11q13. Two highly polymorphic microsatellite markers have been identified within this region and hav...

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β3-adrenergic-receptor allele distributions in children, adolescents and young adults with obesity, underweight or anorexia nervosa

Cited by 78 publications

References 18 publications

Meta-analysis of the association of the Trp64Arg polymorphism in the β3 adrenergic receptor with body mass index

Meta-analysis of the association of the Trp64Arg polymorphism in the β3 adrenergic receptor with body mass index

Gene–gene interaction between PPARγ2 and ADRβ3 increases obesity risk in children and adolescents

Association between a marker in the UCP-2/UCP-3 gene cluster and genetic susceptibility to anorexia nervosa

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