College of Traditional Chinese Medicine, Hainan Medical University, Haikou, 571199, China.
Heilongjiang Academy of Chinese Medicine, Harbin, 150036, Heilongjiang, China.
Sci Rep. 2024 Sep 6;14(1):20803. doi: 10.1038/s41598-024-70711-0.
To investigate the association between single nucleotide polymorphism (SNP) at the rs3918188, rs1799983 and rs1007311 loci of the endothelial nitric oxide synthase (eNOS) gene and genetic susceptibility to systemic lupus erythematosus (SLE) in northeastern China. The base distribution of eNOS gene rs3918188, rs1799983 and rs1007311 in 1712 human peripheral blood samples from Northeast China was detected by SNaPshot sequencing technology. The correlation between genotype, allele and gene model of these loci of the eNOS gene and the genetic susceptibility to SLE was investigated by logistic regression analysis. The results of the differences in the frequency distribution of their gene models were visualised using R 4.3.2 software. Finally, HaploView 4.2 software was used to analyse the relationship between the haplotypes of the three loci mentioned above and the genetic susceptibility to SLE. A multifactor dimensionality reduction (MDR) analysis was used to determine the best SNP-SNP interaction model. The CC genotype and C allele at the rs3918188 locus may be a risk factor for SLE (CC vs AA: OR = 1.827, P < 0.05; C vs A: OR = 1.558, P < 0.001), and this locus increased the risk of SLE in the dominant model and the recessive model (AC + CC vs AA: OR = 1.542, P < 0.05; CC vs AA + AC: OR = 1.707, P < 0.001), while the risk of SLE was reduced in the overdominant model (AC vs AA + CC: OR = 0.628, P < 0.001). The GT genotype and T allele at locus rs1799983 may be a protective factor for SLE (GT vs GG: OR = 0.328, P < 0.001; T vs G: OR = 0.438, P < 0.001) and this locus reduced the risk of SLE in the overdominant model (GT vs GG + TT: OR = 0.385, P < 0.001). There is a strong linkage disequilibrium between the rs1007311 and rs1799983 loci of the eNOS gene. Among them, the formed haplotype AG increased the risk of SLE compared to GG. AT and GT decreased the risk of SLE compared to GG. In this study, the eNOS gene rs3918188 and rs1799983 loci were found to be associated with susceptibility to SLE. This helps to deeply explore the mechanism of eNOS gene and genetic susceptibility to SLE. It provides a certain research basis for the subsequent exploration of the molecular mechanism of these loci and SLE, as well as the early diagnosis, treatment and prognosis of SLE.
为了研究内皮型一氧化氮合酶（eNOS）基因 rs3918188、rs1799983 和 rs1007311 单核苷酸多态性（SNP）与系统性红斑狼疮（SLE）遗传易感性之间的关系。采用 SNaPshot 测序技术检测了来自中国东北地区的 1712 个人外周血样本中 eNOS 基因 rs3918188、rs1799983 和 rs1007311 的碱基分布。通过 logistic 回归分析研究了这些 eNOS 基因座的基因型、等位基因和基因模型与 SLE 遗传易感性之间的相关性。使用 R 4.3.2 软件可视化了这些基因模型频率分布的差异。最后，使用 HaploView 4.2 软件分析了上述三个基因座的单倍型与 SLE 遗传易感性之间的关系。使用多因素维度缩减（MDR）分析来确定最佳 SNP-SNP 相互作用模型。rs3918188 基因座的 CC 基因型和 C 等位基因可能是 SLE 的危险因素（CC 与 AA：OR=1.827，P<0.05；C 与 A：OR=1.558，P<0.001），并且该基因座在显性和隐性模型中增加了 SLE 的风险（AC+CC 与 AA：OR=1.542，P<0.05；CC 与 AA+AC：OR=1.707，P<0.001），而在超显性模型中降低了 SLE 的风险（AC 与 AA+CC：OR=0.628，P<0.001）。rs1799983 基因座的 GT 基因型和 T 等位基因可能是 SLE 的保护因素（GT 与 GG：OR=0.328，P<0.001；T 与 G：OR=0.438，P<0.001），并且该基因座降低了 SLE 在超显性模型中的风险（GT 与 GG+TT：OR=0.385，P<0.001）。eNOS 基因的 rs1007311 和 rs1799983 基因座之间存在很强的连锁不平衡。其中，形成的单倍型 AG 与 GG 相比增加了 SLE 的风险。AT 和 GT 与 GG 相比降低了 SLE 的风险。在这项研究中，发现 eNOS 基因 rs3918188 和 rs1799983 基因座与 SLE 的易感性有关。这有助于深入探讨 eNOS 基因和 SLE 遗传易感性的机制。为后续探索这些基因座和 SLE 的分子机制，以及 SLE 的早期诊断、治疗和预后提供了一定的研究基础。
