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.
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.
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.
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.
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.
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.
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.
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.
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 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.
Leptin [ELISA: SMD (95% CI): -3.03 (-4, -2.06)], radioimmunoassay [RIA: -3.84 (-4.71, -2.98)] and resistin [-1.67 (-2.85, -0.48)] were significantly lower in patients with AN compared with controls, whereas visfatin decrease did not reach significance (-2.03 (-4.38, 0.3).
Thus, the <i>anx/anx</i> mouse shares several characteristics with patients with AN, including emaciation, starvation, premature death, diabetic features, increased FFA and low leptin, and is therefore a unique resource in research on the (neuro)biology of AN.
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.