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Accumulating evidence suggests that altered immunity contributes to the
development of major depressive disorder (MDD).
To examine whether complement factor H (CFH), a regulator of activation
of the alternative pathway of the complement cascade, confers
susceptibility to MDD.
Expression analyses were tested in 53 unmedicated people with MDD and 55
healthy controls. A two-stage genetic association analysis was performed
in 3323 Han Chinese with or without MDD. Potential associations between
CFH single nucleotide polymorphisms and age at MDD
onset were evaluated.
CFH levels were significantly lower in the MDD group at
both protein and mRNA levels (P = 0.009 and
P = 0.014 respectively). A regulatory variant in the
CFH gene, rs1061170, showed statistically significant
genotypic and allelic differences between the MDD and control groups
(genotypic P = 0.0005, allelic P =
0.0001). Kaplan–Meier survival analysis showed that age at onset of MDD
was significantly associated with the C allele of
rs1061170 (log rank statistic χ2 = 6.82, P =
0.009). The C-allele carriers had a younger age at onset
of MDD (22.2 years, s.d. = 4.0) than those without the C
allele (23.6 years, s.d. = 4.3).
CFH is likely to play an important role in the
development of MDD. rs1061170 has an important effect on age at onset of
MDD in Han Chinese and may therefore be related to early pathogenesis of
MDD, although further study is needed.
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