Institute of Medicine, Immanuel Kant Baltic Federal University, Kaliningrad, Russia.
Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, Russia.
Int J Obes (Lond). 2018 Dec;42(12):2036-2046. doi: 10.1038/s41366-018-0124-z. Epub 2018 Jun 15.
BACKGROUND/OBJECTIVES: The 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/METHODS: We 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.
The 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).
These 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.
背景/目的：与普通人群相比，精神分裂症（SCH）患者的代谢综合征（MetS）频率明显更高。本研究的目的是评估内皮型一氧化氮合酶（NOS3）基因中的 T-786C（rs2070744）、G894T（rs1799983）和 C774T（rs1549758）遗传变异及其单倍型是否与俄罗斯人群中 SCH 患者或健康受试者的 MetS 风险相关。
受试者/方法：我们进行了两项病例对照比较。NOS3 多态性在 70 名患有 MetS 的 SCH 患者、190 名体重正常的 SCH 患者、155 名 MetS 患者和 100 名健康对照者中进行了基因分型。MetS 按照国际糖尿病联合会（IDF）提出的标准进行定义。所有样本均测量了人体测量、临床、生化参数和血清亚硝酸盐浓度。使用 Haploview 4.2 进行单倍型频率估计和连锁不平衡测量。
与体重正常的 SCH 患者相比，患有 MetS 的 SCH 患者中 T-786C 多态性的 C 等位基因（P=0.009）和 TT 基因型（P=0.008）频率更高。与 CC 基因型相比，患有 MetS 的 SCH 患者携带 T-786C TT 基因型的血清总胆固醇水平更低（P=0.016）。此外，与健康对照组相比，非 SCH 个体中 774T/894T 单倍型更为常见（P=0.0004，优势比=2.18，95%置信区间 1.4-3.37）。相反，MetS 患者中最常见的单倍型 774C/894G 比健康对照组更为少见（P=0.013，优势比=0.61，95%置信区间 0.41-0.9）。
这些结果表明，NOS3 T-786C 启动子多态性与 SCH 患者的 MetS 风险密切相关。此外，由 G894T 和 C774T 多态性组成的单倍型与俄罗斯人群的 MetS 易感性相关。
