A Preliminary Genetic Analysis of Complement 3 Gene and Schizophrenia

Ni, Jiazuan; Hu, Shuangfei; Zhang, Jiangtao; Tang, Wenxin; Lü, Wei; Zhang, Chen

doi:10.1371/journal.pone.0136372

Cited by 18 publications

(12 citation statements)

References 37 publications

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“…A preliminary investigation on the association of 5 SNPs (rs2277984, rs7951, rs11672613, rs2230205, and rs2230199) in C3 with SCZ found no significant association between these SNPs and SCZ [16]. In our study, we increased the number of subjects and studied the association of 10 tag SNPs (rs11569562, rs344555, rs2241393, rs2241392, rs11569514, rs445750, rs451760, rs11672613, rs2230205, and rs2250656) in C3 with SCZ.…”

Section: Discussionmentioning

confidence: 86%

“…Due to the importance of C3 in multiple immunoregulatory processes, the investigation of C3 polymorphisms remains of interest in SCZ research. However, a handful of genetic studies have been performed to study the association between single nucleotide polymorphisms (SNPs) in C3 and SCZ, but no significant association has been discovered [16]. In this study, we selected 10 SNPs of C3 (rs11569562, rs344555, rs2241393, rs2241392, rs11569514, rs445750, rs451760, rs11672613, rs2230205, and rs2250656) to examine the association between C3 variation and SCZ.…”

Section: Introductionmentioning

confidence: 99%

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Association Between Polymorphisms of the Complement 3 Gene and Schizophrenia in a Han Chinese Population

Zhang

Zhou

et al. 2018

Cell Physiol Biochem

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Background/Aims: Schizophrenia is a severe psychiatric disorder, and complement 3 (C3) is closely related to schizophrenia. We investigated the association between C3 polymorphisms and schizophrenia in a Northeast Han Chinese population. Methods: A total of 2240 Chinese people, consisting of 1086 patients with schizophrenia and 1154 healthy controls, were recruited for this study. Ten single nucleotide polymorphisms (SNPs; rs11569562, rs344555, rs2241393, rs2241392, rs11569514, rs445750, rs451760, rs11672613, rs2230205, and rs2250656) in C3 were selected and genotyped. Results: Genotype distribution analysis indicated that rs11569514 was significantly associated with schizophrenia. In the dominant model (AA vs. GG+GA genotypes), we found a significant protective effect for rs344555 against schizophrenia (odds ratio [OR]: 0.72, 95% confidence interval [CI]: 0.53–0.99, P = 0.04). In the codominant model (TT vs. AA), we found a significant risk effect for rs11569514 on schizophrenia (OR: 4.39, 95% CI: 2.06–9.37, P < 0.001). Haplotypes, including TG (rs11569562 and rs344555), TGG (rs11569562-rs344555-rs2241393), AG (rs344555-rs2241393), CGGGT (rs11569562-rs344555-rs2241393-rs2241392-rs11569514), and ACGTG (rs11569514-rs445750-rs451760-rs11672613-rs2230205), showed either a risk or protective role for schizophrenia. Conclusions: SNP rs11569514 in C3 and haplotypes of C3 variants were associated with schizophrenia in a Han Chinese population.

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Section: Discussionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Association Between Polymorphisms of the Complement 3 Gene and Schizophrenia in a Han Chinese Population

Zhang

Zhou

et al. 2018

Cell Physiol Biochem

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“…First, the lack of a significant association between rs1064395 and schizophrenia may be caused by the modest sample size, possibly resulting in a type II error 44. Accordingly, our findings should be considered only preliminary and will require further investigations for validation in independent samples.…”

Section: Discussionmentioning

confidence: 95%

The <em>NCAN</em> gene: schizophrenia susceptibility and cognitive dysfunction

Wang

Cai

et al. 2016

NDT

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BackgroundCognitive dysfunction has been recognized as a cardinal feature of schizophrenia. Elucidating the neurobiological substrates of cognitive dysfunction in schizophrenia would help identify the underlying mechanism of this disorder. The rs1064395 single nucleotide polymorphism, within the gene encoding neurocan (NCAN), is reported to be associated with schizophrenia in European populations and may influence brain structure in patients with schizophrenia.MethodsIn this study, we aimed to explore whether NCAN rs1064395 confers some risk for schizophrenia and cognitive dysfunction in Han Chinese. We recruited 681 patients with schizophrenia and 699 healthy subjects. Two hundred and fifty-four patients were evaluated according to Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).ResultsThere were no significant differences in genotype or allele distributions of the rs1064395 polymorphism between the schizophrenia and control groups. Patients showed significantly poorer performance than controls on immediate memory, visuospatial skill, language, attention, delayed memory, and total RBANS score. Patients with the A/A or A/G genotype of rs1064395 had lower scores of immediate memory, visuospatial skill, attention, and total RBANS score than those with the G/G genotype. We performed an expression quantitative trait loci analysis and observed a significant association between rs1064395 and NCAN expression in the frontal (P=0.0022, P=0.022 after Bonferroni correction) and cerebellar cortex (P=0.0032, P=0.032 after Bonferroni correction).ConclusionOur findings indicate that this single nucleotide polymorphism may be a risk factor for cognitive dysfunction in patients with schizophrenia. Further investigations are warranted for validation purposes and to identify the precise mechanism by which rs1064395 influences cognitive performance in patients with schizophrenia.

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“…48 Also at the molecular level, the gene encoding C3 has been reported to be a genetic schizophrenia susceptibility region, 49 whereas others could not confirm this. 50 In SLE patients data are limited. Pego-Reigosa et al reported low C3 levels in 4/10 patients with lupus psychosis and no other complement alterations were found.…”

Section: Discussionmentioning

confidence: 99%

Complement levels and anti-C1q autoantibodies in patients with neuropsychiatric systemic lupus erythematosus

Magro-Checa

Schaarenburg

Beaart

et al. 2016

Lupus

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Objective: The objective of this paper is to analyse serum levels of anti-C1q, C1q circulating immune complexes (CIC), complement activation and complement components in systemic lupus erythematosus (SLE) patients during the first central nervous system neuropsychiatric (NP) event and to define the possible association between these results and clinical and laboratory characteristics. Methods: A total of 280 patients suspected of having NP involvement due to SLE were recruited in the Leiden NPSLE-clinic. All SLE patients were classified according to the ACR 1982 revised criteria for the classification of SLE. The clinical disease activity was measured by the SLE Disease Activity Index 2000 (SLEDAI-2K) and NP diagnoses were classified according to the 1999 ACR case definitions for NPSLE. We measured in serum of all patients anti-C1q and C1q CIC levels, the activation capacity of complement (CH50 and AP50) and different complement components (C1q, C3, C4). Results: In 92 patients the symptoms were attributed to SLE. NPSLE patients consisted of 63 patients with focal NPSLE and 34 patients with diffuse NPSLE. Anti-C1q antibodies were significantly higher and CH50, AP50 and C3 were significantly lower in NPSLE patients compared with SLE patients without NPSLE. This association was specially marked for diffuse NPSLE while no differences were found for focal NPSLE. After using potential predictors, decreased C4 remained significantly associated with focal NPSLE, but only when antiphospholipid antibodies (aPL) were included in the model. C3 and AP50 were independently associated with diffuse NPSLE. When SLEDAI-2K was included in the model these two associations were lost. When individual NPSLE syndromes were analysed, psychosis and cognitive dysfunction showed significantly lower values of complement activation capacity and all complement components. No significant associations were seen for other individual NPSLE syndromes. Conclusion: The associations between diffuse NPSLE and anti-C1q, C3/AP50 and focal NPSLE and C4 may be explained by disease activity and the presence of aPL, respectively. The role of complement activation and complement components in lupus psychosis and cognitive dysfunction merits further research. Lupus (2016) 25, 878-888.

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A Preliminary Genetic Analysis of Complement 3 Gene and Schizophrenia

Cited by 18 publications

References 37 publications

Association Between Polymorphisms of the Complement 3 Gene and Schizophrenia in a Han Chinese Population

Association Between Polymorphisms of the Complement 3 Gene and Schizophrenia in a Han Chinese Population

The <em>NCAN</em> gene: schizophrenia susceptibility and cognitive dysfunction

Complement levels and anti-C1q autoantibodies in patients with neuropsychiatric systemic lupus erythematosus

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