Support for the involvement of the KCNK2 gene in major depressive disorder and response to antidepressant treatment.

OBJECTIVE: The aim of this study was to examine the associations between genetic variations in the human KCNK2 gene and major depressive disorder (MDD) and response to antidepressant treatment.

METHOD: Four hundred and forty-nine patients with MDD and 421 normal controls were included in the study; among the MDD patients, 158 were further followed-up for 8 weeks to assess their response to antidepressant treatment. Five polymorphisms (rs12131478, rs6667764, rs10494994, rs11583745 and rs6686529) of the KCNK2 gene were investigated in terms of their association with MDD and antidepressant treatment efficacy.

RESULTS: The genotype frequency of rs6686529 differed significantly between the MDD patients and controls (uncorrected P = 0.00052) and remained statistically significant after correction for multiple comparisons. Individuals with homozygous genotypes (CC or GG) showed greater susceptibility to MDD than those with heterozygous genotypes, indicating a possible heterosis effect of the polymorphism on MDD. In addition, this polymorphism also affected the efficacy of antidepressant treatment: the CC carriers had a greater probability of achieving remission after 8 weeks of treatment than the G-allele carriers [odds ratio = 2.55 (95% confidence interval = 1.11-5.88)].

CONCLUSION: Our findings are in line with those of animal studies, and show that KCNK2 is related to the susceptibility to MDD, and involved in antidepressant treatment response. However, the finding of heterosis association of rs6686529 and MDD may be mechanistic, and further replication studies will be essential.