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Association of TMEM18 variants with BMI and waist circumference in children and correlation of mRNA expression in the PFC with body weight in rats.

ABSTRACT: Genome-wide association studies have shown a strong association of single-nucleotide polymorphisms (SNPs) in the near vicinity of the TMEM18 gene. The effects of the TMEM18-associated variants are more readily observed in children. TMEM18 encodes a 3TM protein, which locates to the nuclear membrane. The functional context of TMEM18 and the effects of its associated variants are as of yet undetermined. To further explore the effects of near-TMEM18 variants, we have genotyped two TMEM18-associated SNPs, rs6548238 and rs4854344, in a cohort of 2352 Greek children (Healthy Growth Study). Included in this study are data on anthropomorphic traits body weight, BMI z-score and waist circumference. Also included are dietary energy and macronutrient intake as measured via 24-h recall interviews. Major alleles of rs6548238 and rs4854344 were significantly associated with an increased risk of obesity (odds ratio = 1.489 (1.161-1.910) and 1.494 (1.165-1.917), respectively), and positively correlated to body weight (P = 0.017, P = 0.010) and waist circumference (P = 0.003, P = 0.003). An association to energy and macronutrient intake was not observed in this cohort. We also correlated food intake and body weight in a food choice model in rats to Tmem18 expression in central regions involved in feeding behavior. We observed a strong positive correlation between TMEM18 expression and body weight in the prefrontal cortex (PFC) (r = 0.5694, P = 0.0003) indicating a potential role for TMEM18 in higher functions related to feeding involving the PFC.

SUBMITTER: Rask-Andersen M

PROVIDER: S-EPMC3262189 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Association of TMEM18 variants with BMI and waist circumference in children and correlation of mRNA expression in the PFC with body weight in rats.

Rask-Andersen Mathias M Jacobsson Josefin A JA Moschonis George G Chavan Rohit A RA Sikder Md Abu Noman MA Allzén Elin E Alsiö Johan J Chrousos George P GP Manios Yannis Y Fredriksson Robert R Schiöth Helgi B HB

European journal of human genetics : EJHG 20110928 2

Genome-wide association studies have shown a strong association of single-nucleotide polymorphisms (SNPs) in the near vicinity of the TMEM18 gene. The effects of the TMEM18-associated variants are more readily observed in children. TMEM18 encodes a 3TM protein, which locates to the nuclear membrane. The functional context of TMEM18 and the effects of its associated variants are as of yet undetermined. To further explore the effects of near-TMEM18 variants, we have genotyped two TMEM18-associated ...[more]

PMID: 21952719

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Project description:BackgroundIn population studies, body mass index (BMI) is generally calculated from self-reported body weight and height. The self-report of these anthropometrics is known to be biased, resulting in a misclassification of BMI status. The aim of our study is to evaluate the accuracy of self-reported weight, height and waist circumference among a Dutch overweight (Body Mass Index [BMI] > or = 25 kg/m2) working population, and to determine to what extent the accuracy was moderated by sex, age, BMI, socio-economic status (SES) and health-related factors.MethodsBoth measured and self-reported body weight and body height were collected in 1298 healthy overweight employees (66.6% male; mean age 43.9 +/- 8.6 years; mean BMI 29.5 +/- 3.4 kg/m2), taking part in the ALIFE@Work project. Measured and self-reported waist circumferences (WC) were available for a sub-group of 250 overweight subjects (70.4% male; mean age 44.1 +/- 9.2 years; mean BMI 29.6 +/- 3.0 kg/m2). Intra Class Correlation (ICC), Cohen's kappa and Bland Altman plots were used for reliability analyses, while linear regression analyses were performed to assess the factors that were (independently) associated with the reliability.ResultsBody weight was significantly (p < 0.001) under-reported on average by 1.4 kg and height significantly (p < 0.001) over-reported by 0.7 cm. Consequently, BMI was significantly (p < 0.001) under-reported by 0.7 kg/m2. WC was significantly (p < 0.001) over-reported by 1.1 cm. Although the self-reporting of anthropometrics was biased, ICC's showed high concordance between measured and self-reported values. Also, substantial agreement existed between the prevalences of BMI status and increased WC based on measured and self-reported data. The under-reporting of BMI and body weight was significantly (p < 0.05) affected by measured weight, height, SES and smoking status, and the over-reporting of WC by age, sex and measured WC.ConclusionResults suggest that self-reported BMI and WC are satisfactorily accurate for the assessment of the prevalence of overweight/obesity and increased WC in a middle-aged overweight working population. As the accuracy of self-reported anthropometrics is affected by measured weight, height, WC, smoking status and/or SES, results for these subgroups should be interpreted with caution. Due to the large power of our study, the clinical significance of our statistical significant findings may be limited.Trial registrationISRCTN04265725.

Dataset Information

Association of TMEM18 variants with BMI and waist circumference in children and correlation of mRNA expression in the PFC with body weight in rats.

Publications

Association of TMEM18 variants with BMI and waist circumference in children and correlation of mRNA expression in the PFC with body weight in rats.

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