Objective: The precise mechanism of major depressive disorder (MDD) is poorly understood. On the basis of the neurotrophin hypothesis, initial findings from our previous studies, and the functions of epidermal growth factor (EGF) in the central nervous system, we proposed that EGF might contribute to the development of MDD, which was investigated in this study.
Methods: Eight single nucleotide polymorphisms (SNPs) within the EGF gene were genotyped in 463 patients with MDD and 413 control participants among a Chinese population; of these, the plasma EGF levels of 210 patients and 223 controls were determined using the enzyme-linked immunosorbent assay. To determine the effect of functional SNPs on EGF secretion in HEK293 cells, EGF levels in the supernatants of cultured cells were also assessed.
Results: None of the informative SNPs showed an allelic association with MDD, but the cis-phase interaction between rs11569017 and rs11569126 was strongly associated with the illness (P=0.0027). The EGF levels in plasma were significantly lower in the patient group than in the control group (P<0.0001). The EGF levels were also significantly lower in patients with the rs11569017-TT genotype than those with either the AA genotype (P=0.013) or the AT genotype (P=0.004); the rs11569017 minor allele significantly affected the expression of the EGF gene (P=0.0004).
Conclusion: The cis-phase interaction between the SNPs within the EGF locus may contribute toward the etiology of MDD. The plasma EGF levels may be a useful biomarker for the early diagnosis, treatment, and prognosis of major psychiatric disorders.