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Two British women studies replicated the association between the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) and BMI.

ABSTRACT: The goal of this study is to investigate the relationship between the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) and body mass index (BMI) in two sizable and well-characterized populations of British women: the British Women's Heart and Health Study (BWHHS) (age 60-79 years) and the mothers from the Avon Longitudinal Study of Parents and Children (age 16-44 years). We genotyped the Val66Met polymorphism (rs6265) in these two populations, and conducted a linear regression analysis to test for an association between this polymorphism and BMI. Both study populations indicated an association between BMI and the Val66Met polymorphism, with individuals carrying the Met-Met genotype having a lower mean BMI than those with the Val-Met or Val-Val genotypes (in the BWHHS): mean BMI difference=-0.911 kg/m(2), 95% confidence interval (CI): -1.70 to -0.12, P=0.023; in the mothers from the Avon Longitudinal Study of Parents and Children (ALSPAC): mean BMI difference=-0.57 kg/m(2), 95%CI: -1.08 to -0.054, P=0.03). In a pooled analysis of these two studies, together with one further published study that provided data in a suitable format for inclusion in our meta-analysis, we found a pooled difference of -0.76 (95% CI: -1.16, -0.036) for adult women; I(2)-test for heterogeneity=51%, P=0.13. Our study indicated an association between BDNF and BMI in two general population studies of women. The exact role of BDNF in weight regulation merits further investigation.

SUBMITTER: Shugart YY

PROVIDER: S-EPMC2986560 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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Two British women studies replicated the association between the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) and BMI.

Shugart Yin Yao YY Chen Lina L Day Ian N M IN Lewis Sarah J SJ Timpson Nicholas J NJ Yuan Wei W Abdollahi Mohammad Reza MR Ring Sue M SM Ebrahim Shah S Golding Jean J Lawlor Debbie A DA Davey-Smith George G

European journal of human genetics : EJHG 20090211 8

The goal of this study is to investigate the relationship between the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) and body mass index (BMI) in two sizable and well-characterized populations of British women: the British Women's Heart and Health Study (BWHHS) (age 60-79 years) and the mothers from the Avon Longitudinal Study of Parents and Children (age 16-44 years). We genotyped the Val66Met polymorphism (rs6265) in these two populations, and conducted a linear regressi ...[more]

PMID: 19209189

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Project description:The purpose of this study was to examine relationships between genetic markers of central serotonin (5-HT) and dopamine function, and risk for post-treatment relapse, in a sample of alcohol-dependent patients.The study included 154 patients from addiction treatment programs in Poland, who met DSM-IV criteria for alcohol dependence. After assessing demographics, severity of alcohol use, suicidality, impulsivity, depression, hopelessness, and severity of alcohol use at baseline, patients were followed for approximately 1 year to evaluate treatment outcomes. Genetic polymorphisms in several genes (TPH2, SLC6A4, HTR1A, HTR2A, COMT, and BDNF) were tested as predictors of relapse (defined as any drinking during follow-up) while controlling for baseline measures.Of 154 eligible patients, 123 (80%) completed follow-up and 48% (n = 59) of these individuals relapsed. Patients with the Val allele in the Val66Met BDNF polymorphism and the Met allele in the Val158Met COMT polymorphism were more likely to relapse. Only the BDNF Val/Val genotype predicted post-treatment relapse [odds ratio (OR) = 2.62; p = 0.019], and time to relapse (OR = 2.57; p = 0.002), after adjusting for baseline measures and other significant genetic markers. When the analysis was restricted to patients with a family history of alcohol dependence (n = 73), the associations between the BDNF Val/Val genotype and relapse (OR = 5.76, p = 0.0045) and time to relapse (hazard ratio = 4.93, p = 0.001) were even stronger.The Val66Met BDNF gene polymorphism was associated with a higher risk and earlier occurrence of relapse among patients treated for alcohol dependence. The study suggests a relationship between genetic markers and treatment outcomes in alcohol dependence. Because a large number of statistical tests were conducted for this study and the literature on genetics and relapse is so novel, the results should be considered as hypothesis generating and need to be replicated in independent studies.

Project description:BACKGROUND In a previous study, we reported that pro-brain-derived neurotrophic factor (proBDNF) was involved in the pathology of alcohol dependence, and the single-nucleotide polymorphism (SNP) Val66Met was located at the prodomain of the brain-derived neurotrophic factor gene (BDNF). This polymorphism has been reported to affect intracellular trafficking and activity-dependent secretion of BDNF. Our present research investigated the relationships between the BDNF Val66Met polymorphism and the plasma levels of proBDNF and mature brain-derived neurotrophic factor (mBDNF) in patients with alcohol dependence. MATERIAL AND METHODS The BDNF gene Val66Met polymorphism was genotyped in 59 alcohol-dependent patients and 37 age- and sex-matched controls, and the plasma levels of proBDNF and mBDNF were assessed by enzyme-linked immunosorbent assay in all participants. RESULTS No association was found between the BDNF gene Val66Met polymorphism and alcohol dependence (P>0.05). In comparison with the control group, the level of plasma proBDNF in the alcohol-dependence group was notably increased (Z=-2.228, P=0.026), while the level of mBDNF was remarkedly decreased (Z=-2.014, P=0.044). In the alcohol-dependence group, significant associations were not found between the Val66Met polymorphisms and proBDNF and mBDNF plasma levels (P>0.05). The plasma level of proBDNF was positively correlated with the average daily alcohol consumption in the last month (r=0.344, P=0.008) and drinking history (r=0.317, P=0.014), while the plasma level of mBDNF had negative effects (r=-0.361, P=0.005, with the average daily alcohol consumption; r=-0.427, P=0.001, with drinking history). CONCLUSIONS The BDNF gene Val66Met polymorphism does not appear to affect the secretion of proBDNF and mBDNF in Chinese patients with alcohol dependence. Furthermore, this study reconfirmed that the plasma levels of proBDNF and mBDNF were correlated with the average daily alcohol consumption in the last month and with drinking history.

Dataset Information

Two British women studies replicated the association between the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) and BMI.

Publications

Two British women studies replicated the association between the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) and BMI.

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