Genetic variants of the inflammatory C‐reactive protein and schizophrenia in Armenian population: a pilot study

Zakharyan, Roksana; Chavushyan, Andranik; Khoyetsyan, Aren; Stahelova, A.; Arakelyan, Arsen; Boyajyan, Anna; Mrázek, František; Petřek, Martin

doi:10.1111/j.1744-313x.2010.00942.x

Cited by 6 publications

(4 citation statements)

References 19 publications

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“…Strikingly, as opposed to the current literature and previous inconclusive small-scale studies [ 66 – 68 ], our findings suggest that genetically elevated levels of CRP are not predisposing but in fact protective for schizophrenia. The significant causal protective role of CRP for schizophrenia was consistent in both IVs using summary statistics, i.e., GRS CRP and GRS GWAS .…”

Section: Discussioncontrasting

confidence: 99%

Investigating the Causal Relationship of C-Reactive Protein with 32 Complex Somatic and Psychiatric Outcomes: A Large-Scale Cross-Consortium Mendelian Randomization Study

et al. 2016

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BackgroundC-reactive protein (CRP) is associated with immune, cardiometabolic, and psychiatric traits and diseases. Yet it is inconclusive whether these associations are causal.Methods and FindingsWe performed Mendelian randomization (MR) analyses using two genetic risk scores (GRSs) as instrumental variables (IVs). The first GRS consisted of four single nucleotide polymorphisms (SNPs) in the CRP gene (GRSCRP), and the second consisted of 18 SNPs that were significantly associated with CRP levels in the largest genome-wide association study (GWAS) to date (GRSGWAS). To optimize power, we used summary statistics from GWAS consortia and tested the association of these two GRSs with 32 complex somatic and psychiatric outcomes, with up to 123,865 participants per outcome from populations of European ancestry. We performed heterogeneity tests to disentangle the pleiotropic effect of IVs. A Bonferroni-corrected significance level of less than 0.0016 was considered statistically significant. An observed p-value equal to or less than 0.05 was considered nominally significant evidence for a potential causal association, yet to be confirmed.The strengths (F-statistics) of the IVs were 31.92–3,761.29 and 82.32–9,403.21 for GRSCRP and GRSGWAS, respectively. CRP GRSGWAS showed a statistically significant protective relationship of a 10% genetically elevated CRP level with the risk of schizophrenia (odds ratio [OR] 0.86 [95% CI 0.79–0.94]; p < 0.001). We validated this finding with individual-level genotype data from the schizophrenia GWAS (OR 0.96 [95% CI 0.94–0.98]; p < 1.72 × 10−6). Further, we found that a standardized CRP polygenic risk score (CRPPRS) at p-value thresholds of 1 × 10−4, 0.001, 0.01, 0.05, and 0.1 using individual-level data also showed a protective effect (OR < 1.00) against schizophrenia; the first CRPPRS (built of SNPs with p < 1 × 10−4) showed a statistically significant (p < 2.45 × 10−4) protective effect with an OR of 0.97 (95% CI 0.95–0.99). The CRP GRSGWAS showed that a 10% increase in genetically determined CRP level was significantly associated with coronary artery disease (OR 0.88 [95% CI 0.84–0.94]; p < 2.4 × 10−5) and was nominally associated with the risk of inflammatory bowel disease (OR 0.85 [95% CI 0.74–0.98]; p < 0.03), Crohn disease (OR 0.81 [95% CI 0.70–0.94]; p < 0.005), psoriatic arthritis (OR 1.36 [95% CI 1.00–1.84]; p < 0.049), knee osteoarthritis (OR 1.17 [95% CI 1.01–1.36]; p < 0.04), and bipolar disorder (OR 1.21 [95% CI 1.05–1.40]; p < 0.007) and with an increase of 0.72 (95% CI 0.11–1.34; p < 0.02) mm Hg in systolic blood pressure, 0.45 (95% CI 0.06–0.84; p < 0.02) mm Hg in diastolic blood pressure, 0.01 ml/min/1.73 m2 (95% CI 0.003–0.02; p < 0.005) in estimated glomerular filtration rate from serum creatinine, 0.01 g/dl (95% CI 0.0004–0.02; p < 0.04) in serum albumin level, and 0.03 g/dl (95% CI 0.008–0.05; p < 0.009) in serum protein level. However, after adjustment for heterogeneity, neither GRS showed a significant effect of CRP level (at p < 0.0016) on any of these outcomes...

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Section: Discussioncontrasting

confidence: 99%

Investigating the Causal Relationship of C-Reactive Protein with 32 Complex Somatic and Psychiatric Outcomes: A Large-Scale Cross-Consortium Mendelian Randomization Study

et al. 2016

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“…A genetic pilot-study aimed at investigating the association of the CRP rs1417938, rs1800947, rs1205 variants with susceptibility to schizophrenia amongst 208 unrelated Armenians (103 patients and 105 healthy controls). However, no significant differences have been found when the proportions of CRP variants were compared between patients and controls (p>.05) [ 65 ].…”

Section: Resultsmentioning

confidence: 99%

“…Regarding the sample, a dis-homogeneous sample has been reported of schizophrenic patients recruited in terms of different socio-demographic characteristics of sample ( i.e ., sex, gender, race, etc . ); some studies specifically recruited some ethnic groups, such as Arabics [ 63 ], Armenians [ 65 ], Egyptians [ 55 , 84 ], Taiwanese [ 67 ], Indians [ 76 ], Japanese [ 78 , 88 ], Chinese [ 81 ], Brazilian [ 82 ], Estonian [ 85 ], Danish [ 86 ], Finnish [ 87 ], which may influence the findings here retrieved. Therefore, the above-mentioned limitations greatly limit the generalizability of findings here reported and have limited the possibility to carry out a clinically significant meta-analysis.…”

Section: Discussionmentioning

confidence: 99%

Protein-C Reactive as Biomarker Predictor of Schizophrenia Phases of Illness? A Systematic Review

Orsolini

Sarchione

Vellante

et al. 2018

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BackgroundSchizophrenia is a complex illness in which genetic, environmental, and epigenetic components have been implicated. However, recently, psychiatric disorders appear to be related to a chronic inflammatory state, at the level of specific cerebral areas which have been found as well impaired and responsible for schizophrenia symptomatology. Hence, a role of inflammatory mediators and cytokines has been as well defined. Accordingly, the role of an acute inflammatory phase protein, the C-reactive protein (CRP) has been recently investigated.ObjectiveThe objective of the present study is to evaluate how PCR may represent a biomarker in schizophrenia, i.e. correlated with illness phases and/or clinical manifestation and/or psychopathological severity.MethodsA systematic review was here carried out by searching the following keywords ((C-reactive protein AND ((schizophrenia) OR (psychotic disorder))) for the topics ‘PCR’ and ‘Schizophrenia’, by using MESH terms.ResultsAn immune dysfunction and inflammation have been described amongst schizophrenic patients. Findings reported elevated CRP levels in schizophrenia, mainly correlated with the severity of illness and during the recrudescent phase. CRP levels are higher when catatonic features, negative symptomatology and aggressiveness are associated. CRP levels appeared not to be related to suicidal behaviour and ideation.ConclusionCRP and its blood levels have been reported higher amongst schizophrenic patients, by suggesting a role of inflammation in the pathogenesis of schizophrenia. Further studies are needed to better understand if CRP may be considered a biomarker in schizophrenia.

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“…BD is now clearly considered as being a multisystem disorder given the elevated burden of medical comorbidities, including cardiovascular disorders, diabetes mellitus, obesity and auto-immune disorders, the majority of them likely related to the often observed immune dysfunction (Leboyer et al 2012 ). According to the dual implication of CRP molecules in both acute and chronic inflammatory processes (Black et al 2004 ) and given the known genetic control governing their production, we investigated here the distribution of three CRP SNPs namely rs 1417938, rs 1130864, and rs 1205, all having functional relevance in terms of CRP expression as suggested by previous studies (Halder et al 2010 ; Ottaviani et al 2011 ; Zacho et al 2008 ; Zakharyan et al 2010 ).…”

Section: Discussionmentioning

confidence: 99%

Association between CRP genetic diversity and bipolar disorder comorbid complications

Boukouaci

Oliveira

Étain

et al. 2018

Int J Bipolar Disord

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BackgroundChronic low-grade inflammation is believed to contribute, at least in a subset of patients, to the development of bipolar disorder (BD). In this context, the most investigated biological marker is the acute phase response molecule, C-reactive protein (CRP). While the genetic diversity of CRP was amply studied in various pathological settings, little is known in BD.Methods568 BD patients along with 163 healthy controls (HC) were genotyped for the following single-nucleotide polymorphisms (SNPs) on the CRP gene: intron rs1417938 (+ 29) T/A, 3′-UTR rs1130864 (+ 1444) G/A, and downstream rs1205 (+ 1846) (C/T). The statistical analysis was performed using Chi-square testing and consisted of comparisons of allele/genotype frequencies between patients and controls and within patient sub-groups according to BD clinical phenotypes and the presence of thyroid disorders.ResultsWe found that the frequencies of the studied SNPs were similar in BD and HC groups. However, the CRP rs1130864 A allele carrier state was significantly more frequent: (i) in BD patients with thyroid disorders than in those without (pc = 0.046), especially among females (pc = 0.01) and independently of lithium treatment, (ii) in BD patients with rapid cycling than in those without (pc = 0.004).ConclusionsOverall, our findings suggest the possibility that CRP genetic diversity may contribute to the development of auto-immune comorbid disorders and rapid cycling, both proxy of BD severity. Such findings, if replicated, may allow to predict complex clinical presentations of the disease, a possible step towards precision medicine in psychiatry.

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Genetic variants of the inflammatory C‐reactive protein and schizophrenia in Armenian population: a pilot study

Cited by 6 publications

References 19 publications

Investigating the Causal Relationship of C-Reactive Protein with 32 Complex Somatic and Psychiatric Outcomes: A Large-Scale Cross-Consortium Mendelian Randomization Study

Investigating the Causal Relationship of C-Reactive Protein with 32 Complex Somatic and Psychiatric Outcomes: A Large-Scale Cross-Consortium Mendelian Randomization Study

Protein-C Reactive as Biomarker Predictor of Schizophrenia Phases of Illness? A Systematic Review

Association between CRP genetic diversity and bipolar disorder comorbid complications

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