A DRD4/BDNF gene-gene interaction associated with maximum BMI in women with bulimia nervosa.
ABSTRACT The goals of the current study were threefold: 1) to examine whether the hypofunctional 7R allele of the DRD4 gene contributes to maximal lifetime body mass in women with BN; 2) to determine whether the BDNF gene contributes to maximal BMI on its own, and 3) to explore possible BDNF/DRD4 gene-gene interactions in mediating maximum lifetime BMIs in BN.
We tested two General Linear Models predicting maximum lifetime BMI with the exon 3 VNTR polymorphism of the dopamine-4 receptor gene (DRD4) and either the Val66Met or the -270C/T polymorphism of BDNF respectively in 163 female probands with BN, purging subtype.
In these bulimic subjects, the hypofunctional 7R allele of DRD4 predicted maximal BMI (p < .01). There was also a significant interaction between the DRD4 gene and the BDNF gene in predicting maximal BMI. The Val66Met rather than the 270C/T polymorphism of BDNF interacting with DRD4 predicted maximum BMI in this BN sample (p < .01). Probands carrying both the hypofunctional 7R allele of DRD4 and the Met66 allele of BDNF had significantly higher maximal BMI than did probands in the other gene-gene interaction groups.
These results provide further evidence that the hypofunctional 7R allele of DRD4 contributes to weight gain in women with BN and that the BDNF gene interacts with DRD4 to influence weight regulation in these subjects.
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ABSTRACT: The brain-derived neurotrophic factor (BDNF) gene may influence eating behavior, body weight and cognitive impairments. We aimed to investigate whether BDNF genetic variability may affect anthropometric and psychological parameters in patients with anorexia or bulimia nervosa (AN, BN) and/or modulate the risk for the disorder. A total of 169 unrelated female patients and 312 healthy controls were genotyped for two common BDNF single-nucleotide polymorphisms (SNPs), Val66Met and C-270T, and several selected tag-SNPs. Associated personality characteristics and psychopathological symptoms were assessed by the EDI-2 and SCL-90R inventories, respectively. No single SNP or haplotype played a relevant role in the risk for AN or BN. The rs16917237 TT genotype was significantly associated with increased weight (74.63 ± 16.58 vs. 57.93 ± 13.02) and body mass index (28.94 ± 6.22 vs. 22.23 ± 4.77) in the BN group after correcting for multiple testing. Haplotype analyses using a sliding window approach with three adjacent SNPs produced four loci of interest. Locus 3 (rs10835210/rs16917237/C-270T) showed a broad impact on the measured psychopathological symptoms. Haplotypes CGC and CGT in this locus correlated with scores in all three scales of the SCL-90R inventory, both in AN and BN patients. In contrast, the results of the EDI-2 inventory were largely unaffected. These preliminary results suggest that variability in the BDNF gene locus may contribute to anthropometric characteristics and also psychopathological symptoms that are common but not exclusive of ED patients.European Child & Adolescent Psychiatry 11/2013; · 3.70 Impact Factor
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ABSTRACT: Although low weight is a key factor contributing to the high mortality in anorexia nervosa (AN), it is unclear how AN patients sustain low weight compared with bulimia nervosa (BN) patients with similar psychopathology. Studies of genes involved in appetite and weight regulation in eating disorders have yielded variable findings, in part due to small sample size and clinical heterogeneity. This study: (1) assessed the role of leptin, melanocortin, and neurotrophin genetic variants in conferring risk for AN and BN; and (2) explored the involvement of these genes in body mass index (BMI) variations within AN and BN. Our sample consisted of 745 individuals with AN without a history of BN, 245 individuals with BN without a history of AN, and 321 controls. We genotyped 20 markers with known or putative function among genes selected from leptin, melanocortin, and neurotrophin systems. There were no significant differences in allele frequencies among individuals with AN, BN, and controls. AGRP rs13338499 polymorphism was associated with lowest illness-related BMI in those with AN (p = 0.0013), and NTRK2 rs1042571 was associated with highest BMI in those with BN (p = 0.0018). To our knowledge, this is the first study to address the issue of clinical heterogeneity in eating disorder genetic research and to explore the role of known or putatively functional markers in genes regulating appetite and weight in individuals with AN and BN. If replicated, our results may serve as an important first step toward gaining a better understanding of weight regulation in eating disorders.Journal of psychiatric research 04/2014; · 3.72 Impact Factor
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ABSTRACT: The dopamine D4 receptor gene (DRD4) encodes a receptor for dopamine, a chemical messenger used in the brain. One variant of the DRD4 gene, the 7R allele, is believed to be associated with attention deficit hyperactivity disorder (ADHD). The aim of this study was to investigate the relationships between repeat polymorphisms in dopamine DRD4 and second language learning styles such as visual (seeing), tactile (touching), auditory (hearing), kinesthetic (moving) and group/individual learning styles, as well as the relationships among DRD4 gene polymorphisms and ADHD in undergraduate students. A total of 227 students between the ages of 17-21 years were evaluated using the wender utah rating scale and DSM-IV diagnostic criteria for ADHD. Additionally, Reid's perceptual learning style questionnaire for second language learning style was applied. In addition, these students were evaluated for social distress factors using the list of Threatening Events (TLE); having had no TLE, having had just one TLE or having had two or more TLEs within the previous 6 months before the interview. For DRD4 gene polymorphisms, DNA was extracted from whole blood using the standard phenol/chloroform method and genotyped using polymerase chain reaction. Second language learners with the DRD4.7+ repeats showed kinaesthetic and auditory learning styles, while students with DRD4.7-repeats showed visual, tactile and group learning, and also preferred the more visual learning styles [Formula: see text]. We also demonstrated that the DRD4 polymorphism significantly affected the risk effect conferred by an increasing level of exposure to TLE.Molecular Biology Reports 05/2014; · 2.51 Impact Factor