5-HT(2A) gene promoter polymorphism as a modifying rather than a vulnerability factor in anorexia nervosa

The A allele of the 5-HT(2A) gene (-1438A/G polymorphism) has been associated with anorexia nervosa in four studies, but not in three others. One possibility to explain such a discrepancy is that the A allele acts as a modifying rather than a vulnerability allele. To test this hypothesis, we increased our initial sample of 102 trios left open bracket Mol. Psychiatry 7 (2002) 90 right open bracket with 43 new patients with anorexia nervosa and 98 healthy controls. In addition to confirming the absence of association on the global sample of 145 patients, we found that patients with the A allele had a significantly later age at onset of the disease (P = 0.032). Furthermore, the A allele was also transmitted with an older age at onset (P = 0.023) using a quantitative-trait TDT approach. The A allele may thus act as a modifying factor (delaying onset), potentially explaining variations of allele frequency across samples, in which differences in average age at onset are not only possible, but also expected. Taking into account vulnerability genes, but also genes modifying the expression of the disorder, will help to disentangle the complexity of the etiological factors involved in anorexia nervosa.