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NOS1AP Gene Variants and Their Role in Metabolic Syndrome: A Study of Patients with Schizophrenia.

ABSTRACT: Metabolic syndrome (MetS) is common among schizophrenia patients, and one of MetS's causes may be an imbalance in nitric oxide regulation. In this study, we examined associations of three polymorphic variants of the nitric oxide synthase 1 adapter protein (NOS1AP) gene with MetS in schizophrenia. NOS1AP regulates neuronal nitric oxide synthase, which controls intracellular calcium levels and may influence insulin secretion. The aim of the investigation was to study polymorphic variants of the NOS1AP gene as possible markers of MetS in patients with schizophrenia. A total of 489 Caucasian patients with schizophrenia (ICD-10) from Siberia (Russia) were included in the study, and 131 (26.8%) patients had MetS (IDF classification, 2007). The participants were genotyped for three single-nucleotide polymorphisms in NOS1AP (rs12143842, rs10494366, and rs12029454). Logistic regression was used for association analysis. Single-nucleotide polymorphisms, sex, and age served as covariates; the dependent variable was the coded parameter of the presence/absence of MetS. Polymorphisms rs12143842 and rs10494366 showed a stable association even after Bonferroni's correction for multiple comparisons (p = 0.005 and 0.002, respectively), indicating a statistically significant contribution of these polymorphic variants to the pathogenesis of MetS. Our results suggest that in patients with schizophrenia, NOS1AP may be involved in MetS pathophysiology.

SUBMITTER: Mednova IA

PROVIDER: S-EPMC10968077 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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<i>NOS1AP</i> Gene Variants and Their Role in Metabolic Syndrome: A Study of Patients with Schizophrenia.

Mednova Irina A IA Pozhidaev Ivan V IV Tiguntsev Vladimir V VV Bocharova Anna V AV Paderina Diana Z DZ Boiko Anastasiia S AS Fedorenko Olga Y OY Kornetova Elena G EG Bokhan Nikolay A NA Stepanov Vadim A VA Ivanova Svetlana A SA

Biomedicines 20240312 3

Metabolic syndrome (MetS) is common among schizophrenia patients, and one of MetS's causes may be an imbalance in nitric oxide regulation. In this study, we examined associations of three polymorphic variants of the nitric oxide synthase 1 adapter protein (<i>NOS1AP</i>) gene with MetS in schizophrenia. NOS1AP regulates neuronal nitric oxide synthase, which controls intracellular calcium levels and may influence insulin secretion. The aim of the investigation was to study polymorphic variants of ...[more]

PMID: 38540239

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Project description:Introduction Schizophrenia is associated with lower life expectancy due to cardiovascular disease. Metabolic syndrome (MetS) occupies an important place among the main problems. Indicators of hormones regulating metabolism may be appealing candidates as biomarkers of metabolic side-effects. Certain role belongs to genetic factors that might be the basis of sensitivity to development of MetS. Objectives The aim is to study polymorphisms of leptin gene (LEP) and serum leptin concentration in schizophrenia patients with metabolic syndrome. Methods After obtaining informed consent, patients with schizophrenia (ICD-10: F20) were included: 91 patients for biochemical research and 463 patients for genotyping. Patients were divided into two groups: 46 (119) with MetS; 45 (344) without it. Concentration of leptin was measured on an analyzer MAGPIX (Luminex, USA). Determination of 4 polymorphisms (rs2167270, rs3828942, rs10954173, rs4731426) of LEP was performed by PCR. Differences were considered significant at p<0.05. Results The leptin concentration is significantly (p<0.001) higher in MetS (13511.5 [7392.5; 28278.75] pg/ml) compared to patients without MetS (6662 [2131.5; 11380] pg/ml). Significant differences were found in the distribution of rs3828942 (GG:GA:AA): 25.9%:44%:30.2% in MetS and 31.2%:52.6%:16.2% without MetS (χ2=10.545, p=0.005). The genotype AA and the allele A have a predisposing effect on the development of MetS (OR1=2.247, C.I:1.248-4.046; OR2=1.475, C.I:1.093-1.991, χ2=6.49, p=0.01). Conclusions A number of features are observed in patients with MetS, which impair the functioning of patients. These investigations should aim to optimize the approach to assess the risk of MetS. The study was supported by grants from the RSF 19-75-10012 (genetic research) and 18-15-00011 (determination of leptin concentration) Disclosure The study was supported by grants from the Russian Science Foundation №19-75-10012 (genetic research) and №18-15-00011 (determination of leptin concentration)

Dataset Information

NOS1AP Gene Variants and Their Role in Metabolic Syndrome: A Study of Patients with Schizophrenia.

Publications

<i>NOS1AP</i> Gene Variants and Their Role in Metabolic Syndrome: A Study of Patients with Schizophrenia.

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