Our data show a significant association between polymorphisms with the gene encoding HTR2A with both AN subtypes, an association between polymorphisms within the genes encoding HTR1D and HTR1B with RAN, and an association between polymorphisms within the gene encoding HTR2C with BPAN.
We hypothesized that the 5-HT2A promoter polymorphism, -1438G>A, previously associated with anorexia nervosa, would be more abundant in women with obsessive-compulsive disorder.
We genotyped the -1438 A/G polymorphism in the 5-HT2A receptor gene and serotonin transporter linked-polymorphic region (5-HTTLPR) in 132 adolescent subjects with AN and in 93 healthy controls.
A 5-HT2A receptor promoter polymorphism, -1438G/A, was reported to be significantly increased in patients with anorexia nervosa when compared with controls.
Analysis of the -1438 G/A polymorphism of the 5-HT2A serotonin receptor gene in bulimia nervosa patients with or without a history of anorexia nervosa.
To examine the distribution of different polymorphisms in genes of the 5-HT system in patients with anorexia nervosa (AN) and bulimia nervosa (BN), we analyzed the distribution of a polymorphism (-1438G/A) and the presence of known mutations in 5-HT2A and 5-HT2C receptor genes in 168 Italian female patients affected by AN and BN.
Four studies of a polymorphism (-1438 G/A) within the promoter of the 5-HT(2A) gene (5-HT(2A)) revealed an association of the A-allele to anorexia nervosa.
Thus, at least for Japanese subjects, the A-allele of the -1438G/A polymorphism in the promoter region of the 5-HT2A receptor gene does not contribute to a predisposition to AN.
Analysis of phenotypic variability led to the identification of a specific genetic risk factor that approached genome-wide significance (rs929626 in EBF1 (Early B-Cell Factor 1); P = 2.04 × 10<sup>-7</sup>; OR = 0.7; 95% confidence interval (CI) = 0.61-0.8) with independent replication (P = 0.04), suggesting a variant-mediated dysregulation of leptin signaling may play a role in AN.
To investigate this hypothesis we screened the coding region of the leptin gene and part of the leptin gene linked upstream region (LEGLUR) in 49 patients with AN and 315 children and adolescents with extreme obesity.
A SERT gene genotype with no apparent individual effect on risk and known to be associated with anxiety is preferentially transmitted to children with AN (chi2 trend=9.457, 1 df, P=0.0021) and AN-R alone (chi2 trend=7.477, 1 df, P=0.0063) when the 'more active' MAOA gene variant is also transmitted.
Following on from previous work by our group where we showed that early onset anorexia nervosa (AN) and obsessive-compulsive disorder (OCD) shared a common genetic background, the aim of the present study is to assess genetic pleiotropy related to the serotonergic system (SLC6A4, 5HTR2A, 5HTR2C, TPH2, SLC18A1), in a common phenotype such as very-early age of onset.
Case-control studies also suggest a BDNF contribution in the aetiology of ED: we have previously reported a strong association between the Met66 variant within the BDNF gene, restricting AN (ANR) and minimum body mass index (minBMI) in a Spanish sample, and a positive association between the Val66Met and -270C/TBDNF SNPs and ED in six different European populations.
Although, at present, no convincing evidence for associations of candidate genes with EDs has been provided, the 5-HT(2A) receptor gene and the BDNF gene seem to be promising candidates for genetic influences on AN, since polymorphic variants of these genes have been found quite consistently, although not specifically, linked to AN restricting subtype in large sample studies.
Thus we were unable to replicate the previous findings that the Met66 allele of the BDNF is associated with AN and that the minimum BMI is lower or the harm avoidance score is higher in AN patients with the Met66 allele.