The 5-HT2A –1438 A/G and 5-HTTLPR Polymorphisms and Personality Dimensions in Adolescent Anorexia Nervosa: Association Study

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Abstract
Disturbances of serotonergic neurotransmission and temperamental vulnerability have both been implicated in the pathogenesis of anorexia nervosa (AN). 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. Personality dimensions in AN patients were assessed with the Temperament and Character Inventory. In a case-control model, we tested the hypothesis that these genetic variants confer susceptibility to AN. We also analyzed whether two polymorphisms show association with temperamental and character traits. No significant difference was found in the 5-HTTLPR frequency between AN patients and controls; however, there was a statistical trend towards a higher frequency of the A allele of the –1438 A/G polymorphism in patients than in controls (64.9 vs. 56.7%, χ2 test, p = 0.08). We also found a significant association between the A allele of this polymorphism and two temperamental traits. Patients homozygous for the A allele showed lower reward dependence than G/G homozygotes, and A/A homozygotes showed lower harm avoidance than heterozygotes. Low reward dependence and harm avoidance were more characteristic of the restrictive-type AN than of other subtypes of the disorder. No association of 5-HTTLPR with personality dimensions in AN patients was observed. Our results may suggest that the A allele of the –1438 A/G polymorphism confers some genetic risk for adolescent AN patients, especially in those with personality traits, which are typical of the restrictive-type AN.