Genetic variants of interleukin-10 gene promoter are associated with schizophrenia in Saudi patients: A case-control study

Al-Asmary, Saeed M.; Kadasah, Saeed; Arfin, Misbahul; Tariq, Mohammad; Alasmari, Abdulrahman

doi:10.4103/1947-2714.145466

Cited by 13 publications

(12 citation statements)

References 64 publications

(86 reference statements)

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“…These findings may also point out potential biases in previous studies regarding the causes of elevated CRP levels in SZ patients, such as pleiotropic effects within chosen instruments and/or reverse causality ( 13 ). In addition to CRP variants, other recent studies have identified other variants associated with SZ including variants in the major histocompatibility complex region on Chromosome 6p21 ( 54 ), harboring many cytokine genes ( 55 – 57 ), and in the TNF promoter ( 58 ), IL10 promoter ( 59 ), IL1B ( 60 ) and C4 ( 61 ). To make a long story short, CRP has been robustly associated with the SZ risk, however it remains unclear if this association may be due to confounding factors.…”

Section: Discussionmentioning

confidence: 99%

C-Reactive Protein as a Peripheral Biomarker in Schizophrenia. An Updated Systematic Review

et al. 2018

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Objectives: The objective of this systematic review was to synthetize the published data on the relationships between elevated blood C-reactive protein (CRP) levels and schizophrenia (SZ) onset risk, illness characteristics and treatments, cognition and physical health.Method: The systematic bibliographic searches have been carried out according to the Cochrane methodology. Medline, web of science, Google Scholar with each database being searched from inception to November 2017.Results: 53 studies were included in the present review. While meta-analyses including case-control studies suggest a clear association between CRP and SZ, one other study has suggested that CRP-associated genes were associated with a lower risk of SZ onset. Increased CRP has been significantly associated with positive symptoms in acute phase psychosis, while studies including community-dwelling stabilized subjects did not find such an association. Abnormal CRP has been associated with a wide range of cognitive impairment in SZ stabilized individuals. Body Mass index has been extensively associated with increased CRP in SZ subjects; and increased CRP has been identified as a risk factor for metabolic syndrome and cardiovascular risk in SZ subjects. Increased CRP has also been associated with high nicotine dependence in SZ smokers and one study has suggested that increased CRP was associated with sedentary behavior.Conclusion: In the light of the above-mentioned studies, increased hs-CRP may be reasonably suggested as a marker for SZ onset risk, as well as a risk factor for increased positive symptoms, cognitive impairment, hypovitaminosis D, microbiota disturbances, cardiovascular and metabolic syndrome risk in SZ subjects, and increased nicotine dependence in SZ smokers. In case of increased CRP levels, anti-inflammatory strategies (add-on anti-inflammatory drugs including aspirin and omega 3 fatty acids, vitamin D supplementation, physical activity, probiotics) should be also further evaluated.Limits: Most of the studies were cross-sectional and cohort studies are needed to determine the temporal relationship between increased CRP and the psychiatric outcomes.

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Section: Discussionmentioning

confidence: 99%

C-Reactive Protein as a Peripheral Biomarker in Schizophrenia. An Updated Systematic Review

et al. 2018

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“…The exact mechanism for how elevated CRP levels are linked to schizophrenia requires a well-defined experimental analysis. In addition to CRP variants, other recent studies have identified several inflammatory genetic variants associated with schizophrenia and bipolar disorder, which include variants in the major histocompatibility complex (MHC) region on Chromosome 6p21 [ 72 ]—harboring many cytokine genes [ 54 , 73 – 76 ]—and in the IL10 promoter [ 77 ], TNF promoter [ 78 ], IL1B [ 79 ], and C4 [ 80 ].…”

Section: Discussionmentioning

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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“…Although the frequency of allele G was reported to be slightly higher in Iranian Azeri Turkish IBD patients, it did not reach statistical significance [110]. Further, no association of TNF-α(-308G/A) polymorphism with IBD susceptibility was found in Australian [82], Brazilian [60,130], Canadian [100], Chinese [106,131], Czech [132], French [133], Indian [108], Korean [115], Newfoundland [27], Spanish [126], and Turkish [120] populations. The reason for these differences in the TNF-α genetic associations with IBD etiology might be the variations in sample size, genotyping methods, and/or ethnicity itself as frequencies of alleles and genotypes of TNF-α (-308G/A) also vary in different ethnic healthy populations worldwide [39] ( Table 3).…”

Section: Discussionmentioning

confidence: 99%

“…The -1082G, -819C, and -592C (GCC) alleles have been associated with elevated levels of IL-10 production [78], while ACC and ATA haplotypes show intermediate and low IL-10 gene transcription, respectively [79]. These IL-10 gene polymorphisms are reported to be associated with susceptibility/development to various inflammatory disorders [40,[80][81][82]. However, data are limited and inconsistent and therefore do not allow drawing unequivocal conclusions.…”

Section: Introductionmentioning

confidence: 99%

“…To detect polymorphisms at position -308 and intron 1 +252 of the TNF-α and TNF-β genes, respectively, and at position -592, -819 and -1082 of IL-10 gene, the amplification of TNF-α, TNF-β, and IL-10 genes was performed using an amplification refractory mutation systems PCR methodology described elsewhere [39,93]. PCR amplification was carried out in PuReTaq Ready-to-Go PCR Beads (GE Healthcare, Buckinghamshire, UK) as described earlier [82]. The allele and genotype frequencies of all 5 polymorphisms were evaluated in IBD patients and controls.…”

Section: Polymerase Chain Reaction (Pcr) Amplificationmentioning

confidence: 99%

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Genetic variants of interleukin-10 gene promoter are associated with schizophrenia in Saudi patients: A case-control study

Cited by 13 publications

References 64 publications

C-Reactive Protein as a Peripheral Biomarker in Schizophrenia. An Updated Systematic Review

C-Reactive Protein as a Peripheral Biomarker in Schizophrenia. An Updated Systematic Review

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

Inflammatory Bowel Disease: The Association of Inflammatory Cytokine Gene Polymorphisms

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