Haplotype analysis of endothelial nitric oxide synthase (NOS3) genetic variants and metabolic syndrome in healthy subjects and schizophrenia patients

Abstract

Background/objectivesThe frequency of metabolic syndrome (MetS) is significantly higher in schizophrenia (SCH) patients, when compared to the general populatiotin. The goal of this study was to evaluate whether genetic variants T-786C (rs2070744), G894T (rs1799983) and C774T (rs1549758) in the endothelial nitric oxide (NOS3) gene and/or their haplotypes could be associated with the risk of MetS in SCH patients or healthy subjects from Russian population.Subjects/methodsWe performed two case−control comparisons. NOS3 polymorphisms were genotyped in 70 SCH patients with MetS, 190 normal weight SCH patients, 155 MetS patients, and 100 healthy controls. MetS was defined as per the criteria proposed by the International Diabetes Federation (IDF). Anthropometric, clinical, biochemical parameters, and serum nitrite concentrations were measured in all samples. Haplotype frequency estimations and linkage disequilibrium measures were made using Haploview 4.2.ResultsThe higher C allele (P = 0.009) and lower TT genotype (P = 0.008) frequencies of T-786C polymorphism were found in SCH patients with MetS compared to those in normal weight SCH patients. SCH patients with MetS who were carriers of the T-786C TT genotype had lower serum total cholesterol levels in comparison to the CC genotype (P = 0.016). Furthermore, the 774T/894T haplotype was more frequent in non-SCH individuals with MetS compared to healthy controls (P = 0.0004, odds ratio = 2.18, 95% confidence interval 1.4–3.37). Conversely, the most common haplotype 774C/894G was less frequent in MetS patients than in healthy controls (P = 0.013, odds ratio = 0.61, 95% confidence interval 0.41–0.9).ConclusionsThese results indicate that the NOS3 T-786C promoter polymorphism was closely associated with MetS risk in SCH patients. In addition, the haplotypes composed of G894T and C774T polymorphisms are associated with the MetS susceptibility in Russian population.

Genetic variations associated with coronary artery disease and myocardial infarction in the Arab world: a systematic review and meta-analysis

“…We conducted 46 meta-analyses for 46 variants in 39 genes (Figure 3, Supplementary Figures S1-S46) which demonstrated a potential risk of developing CAD and/or MI. The NOS3: c.894G>T (rs1799983) has previously been shown to be associated with ischemic heart disease [125,126], coronary artery spasm [127], ischemic stroke [128], hypertension [129,130], metabolic syndrome [131], and Alzheimer's disease [132][133][134]. However, the evidence for an association of this SNP with CAD or MI risk remain conflicting and inconclusive, with several studies reporting a lack of association with the disease [135][136][137][138][139][140].…”

Genetic variations associated with coronary artery disease and myocardial infarction in the Arab world: a systematic review and meta-analysis

“…We conducted 46 meta-analyses for 46 variants in 39 genes (Figure 3, Supplementary Figures S1-S46) which demonstrated a potential risk of developing CAD and/or MI. The NOS3: c.894G>T (rs1799983) has previously been shown to be associated with ischemic heart disease [125,126], coronary artery spasm [127], ischemic stroke [128], hypertension [129,130], metabolic syndrome [131], and Alzheimer's disease [132][133][134]. However, the evidence for an association of this SNP with CAD or MI risk remain conflicting and inconclusive, with several studies reporting a lack of association with the disease [135][136][137][138][139][140].…”

Gastrointestinal Dysfunctions Are Associated withIL-10Variants in Parkinson’s Disease

“…The color is defined according to the value of coefficient D′ and logarithm of odds (LOD). If |D'| < 1 and LOD < 2, the color is white; if |D'| < 1 and LOD ≥ 2, the color is pink/red [34].…”