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

Author:

Mednova Irina A.1ORCID,Pozhidaev Ivan V.1ORCID,Tiguntsev Vladimir V.1,Bocharova Anna V.2ORCID,Paderina Diana Z.1ORCID,Boiko Anastasiia S.1ORCID,Fedorenko Olga Y.1ORCID,Kornetova Elena G.1ORCID,Bokhan Nikolay A.1,Stepanov Vadim A.2,Ivanova Svetlana A.1ORCID

Affiliation:

1. Mental Health Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 4 Aleutskaya Str., Tomsk 634014, Russia

2. Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk 634050, Russia

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.

Funder

Russian Science Foundation

Publisher

MDPI AG

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