ObjectiveGender comparison in epidemiological studies has consistently demonstrated a greater prevalence for major depressive disorders (MDD) in females. Several lines of evidence have implicated oestrogen pathways in this gender difference. Furthermore, there is evidence that attempted suicides are more frequent in women. A population-based association study was used to test the hypothesis that the genetic variants (PvuII andXbaI polymorphisms) of the oestrogen receptor &agr; gene (ER-&agr;) confer susceptibility to MDD.MethodsThe ER-&agr; was genotyped for 154 patients with MDD and 226 controls in a Chinese population.ResultsStatistical analysis showed a significant difference in thePvuII genotype and allele frequencies between the female MDD patients and the female controls (P=0.010 andP=0.004, respectively). However, no significant differences in ER-&agr; genotype or allele frequencies were found between male MDD patients and male controls. Furthermore, the ER-&agr; genotypes were not associated with suicide-attempt history for MDD cases.ConclusionsOur results suggest that the ER-&agr; may play a role in the susceptibility of MDD in females.