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Complement factor H and susceptibility to major depressive disorder in Han Chinese
Chen Zhang1, Deng-Feng Zhang1, Zhi-Guo Wu1
1Chen Zhang, MD, PhD, Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai and Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan; Deng-Feng Zhang, PhD, Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan; Zhi-Guo Wu, MD, PhD, Dai-Hui Peng, MD, PhD, Jun Chen, MD, PhD, Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai; Jianliang Ni, MD, Department of Psychiatry, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang; Wenxin Tang, MD, Hangzhou Seventh People's Hospital, Hangzhou, Zhejiang; Lin Xu, PhD, Yong-Gang Yao, PhD, Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan and CAS Center for Excellence in Brain Science, Chinese Academy of Sciences, Shanghai; Yi-Ru Fang, MD, PhD, Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Background:
Accumulating evidence suggests that altered immunity contributes to the development of major depressive disorder (MDD).
Aims:
To examine whether complement factor H (CFH), a regulator of activation of the alternative pathway of the complement cascade, confers susceptibility to MDD.
Method:
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.
Results:
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 χ(2) = 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).
Conclusions:
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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