Association of unipolar depression with gene polymorphisms in the serotonergic pathways in Han Chinese

The present study aims to investigate the association of unipolar depression (UPD) with six serotonergic gene polymorphisms in Han Chinese.

One hundred and thirty-two UPD patients and 180 healthy controls were genotyped for polymorphisms of six serotonergic genes, including tryptophan hydroxylase (TPH1 A218C), serotonin transporter promoter region (5-HTTLPR), serotonin receptor 2A (5-HT2AR -1438G/A), serotonin receptor 2C (5-HT2CR Cys23Ser), serotonin receptor 6 (5-HT6R C267T) and serotonin receptor 1Dβ (5-HT1DβR T371G). Symptomatic clusters were evaluated by the 24-item Hamilton Rating Scale for Depression (HAMD).

The frequencies of S/S genotype and S allele in 5-HTTLPR polymorphism were significantly higher in UPD patients than in healthy controls. There was a significant difference in distributions of genotypes in 5-HT2CR Cys23Ser polymorphism between UPD patients and control subjects, but the difference became no significant when the data were further stratified by gender. The patients with genotypes G/G and T/G of 5-HT1DβR T371G polymorphism had significantly lower scores of diurnal variation evaluated by HAMD than those with genotype T/T, while the patients with genotype T/G had significantly higher scores of hopelessness than those with genotypes G/G and T/T. There were no significant differences in genotypic and allelic distributions of TPH1 A218C, 5-HT2AR -1438G/A or 5-HT6R C267T polymorphisms between the case and control groups.

The study demonstrates that 5-HTTLPR and 5-HT2CR Cys23Ser polymorphisms might contribute to susceptibility of UPD, and the genotype T/T in 5-HT1DβR T371G polymorphism might be a risk factor for diurnal variation, while T/G might be a protective factor against hopelessness in Han Chinese populations.