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Metabolic syndrome is negatively associated with cognition among endothelial nitric oxide synthase (eNOS)- 786C carriers in schizophrenia-spectrum disorders.

ABSTRACT: Although metabolic syndrome and cognitive inefficiencies are well-described common complications of schizophrenia, their association remains inconsistent, potentially due to poorly understood mechanisms underlying their relationship. Variability in the endothelial nitric oxide synthase (eNOS) gene, specifically the T-786C variant, has been separately associated with cognition and metabolic syndrome, with worse outcomes for eNOS-786C carriers likely occurring via negative effects on blood vessel functioning. However, the interaction between eNOS and metabolic syndrome in cognition among adults with schizophrenia is unknown. This study aimed to test the main and interaction effects of the eNOS-786C allele in cognition using hierarchical regression analyses controlling for age, sex, education, race, and antipsychotic exposure. Metabolic syndrome, eNOS T-786C genotype, and cognitive performance were assessed in 226 community-dwelling participants with chronic schizophrenia-spectrum disorders. Results demonstrated a significant interaction between metabolic syndrome and the eNOS-786C allele. Specifically, among eNOS-786C carriers only, metabolic syndrome was independently associated with lower scores in processing speed and verbal fluency, and predicted 12.5% and 15.8% of variance in performance, respectively. These results suggest that the additive negative effects of eNOS-786C and metabolic syndrome on blood vessel functioning may be severe enough to negatively impact cognition. The finding that metabolic syndrome is associated with worse cognition only in the presence of the eNOS-786C allele may clarify extant inconsistencies in the literature. These findings provide preliminary evidence that may inform interventions to reduce cognitive morbidity among adults with schizophrenia.

SUBMITTER: Kraal AZ

PROVIDER: S-EPMC6707862 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Metabolic syndrome is negatively associated with cognition among endothelial nitric oxide synthase (eNOS)- 786C carriers in schizophrenia-spectrum disorders.

Kraal A Zarina AZ Moll Allison C AC Arvanitis Nicole R NR Ward Kristen M KM Dougherty Ryan J RJ Grove Tyler B TB Burghardt Kyle J KJ Ellingrod Vicki L VL

Journal of psychiatric research 20190726

Although metabolic syndrome and cognitive inefficiencies are well-described common complications of schizophrenia, their association remains inconsistent, potentially due to poorly understood mechanisms underlying their relationship. Variability in the endothelial nitric oxide synthase (eNOS) gene, specifically the T-786C variant, has been separately associated with cognition and metabolic syndrome, with worse outcomes for eNOS-786C carriers likely occurring via negative effects on blood vessel ...[more]

PMID: 31421598

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Project description:AIM:To investigate the role of endothelial nitric oxide synthase -786T > C promoter polymorphism in the etiology of gastric cancer (GC). METHODS:A total of 150 GC patients and 150 control subjects were included in the study. The information on demographic features was elicited with an informed consent from all the patients and control subjects using a structured questionnaire. Helicobacter pylori (H. pylori) infectivity status was tested in antral biopsies from all the subjects by rapid urease test following the method of Vaira et al. Genomic DNA was isolated from whole blood samples following the salting out method of Lahiri et al. Genotype analysis of the rs2070744 polymorphism was carried out by allele-specific polymerase chain reaction method. The genotypes were determined based on the appearance of bands on an agarose gel stained with ethidium bromide under ultraviolet gel documentation with the help of 100 bp ladder. Odds ratios and corresponding 95%CIs were determined using java stat online software. RESULTS:There was a significant difference in the distribution of C allele (C vs T; P = 0.000, OR = 5.038) in patient group compared to the control subjects exhibiting a fivefold increased risk for GC. When the T/T and C/C genotypes were compared, there was an enhanced GC risk for individuals with C/C genotype (T/T vs C/C; P = 0.000). Among the demographic factors, smoking and alcoholism were the common risk factors in patients compared to the control subjects (P < 0.05). Patients with smoking and alcoholism developed cancer even in heterozygous T/C condition (smoking: P = 0.020 and alcoholism: P = 0.005). Individuals with H. pylori infection showed seven fold increased risk for cancer. All the patients with C/C genotype revealed a significant association between H. pylori infection and GC. Among the patients 2.4% of them revealed familial incidence of GC. No significant difference was noticed between cases and controls with regard to consanguinity (P = 0.473). CONCLUSION:The Present data suggest that eNOS-786 C/C genotype and C allele may be considered as potential risk factors in patients with GC.

Project description:BackgroundSeveral meta-analyses of the relationship between endothelial nitric oxide synthase (eNOS) T-786C gene polymorphism and chronic kidney disease (CKD) have been published. However, the results of these studies were inconsistent, and it is undetermined whether sample sizes are sufficient to reach a definite conclusion.ObjectiveTo elucidate the relationship between T-786C and CKD by combining previous studies with our case-control sample and incorporate trial sequential analysis (TSA) to verify whether the sample size is adequate to draw a definite conclusion.MethodsPubMed and Embase databases were searched for relevant articles on eNOS T-786C and CKD before February 28, 2021. TSA was also incorporated to ascertain a conclusion. A total of 558 hemodialysis cases in the case-control study was recruited from nine dialysis centers in the northern area of Taiwan in 2020. Additionally, 640 healthy subjects of the control group, with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2, were selected from participants of the annual elderly health examination program at the Tri-Service General Hospital. The functional analysis was based on eQTL data from GTExPortal.ResultsAfter screening with eligibility criteria, 15 papers were included and eventually combined in a meta-analysis. The result of the TSA showed that the sample size for Caucasians was adequate to ascertain the correlation between eNOS T-786C and CKD but was insufficient for Asians. Therefore, we added our case-control samples (n = 1198), though not associated with CKD (odds ratio [OR] = 1.01, 95% confidence interval [CI] = 0.69-1.46), into a meta-analysis, which supported that eNOS T-786C was significantly associated with CKD in Asians (OR = 1.39, 95% CI = 1.04-1.85) by using an adequate cumulative sample size (n = 4572) analyzed by TSA. Data of eQTL from GTEx showed that T-786C with the C minor allele exhibited relatively lower eNOS mRNA expression in whole blood, indicating the hazardous role of eNOS T-786C in CKD.ConclusionseNOS T-786C genetic polymorphism was of conclusive significance in the association with CKD among Asians in our meta-analysis. Our case-control samples play a decisive role in changing conclusions from indefinite to definite.

Dataset Information

Metabolic syndrome is negatively associated with cognition among endothelial nitric oxide synthase (eNOS)- 786C carriers in schizophrenia-spectrum disorders.

Publications

Metabolic syndrome is negatively associated with cognition among endothelial nitric oxide synthase (eNOS)- 786C carriers in schizophrenia-spectrum disorders.

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