The purpose of this study was to analyse the effect of the T-786C polymorphism and intron 4 27 bp variable number tandem repeat(VNTR) eNOS markers for their potential association with Systemic Lupus Erythematosus(SLE), Hashimotos thyroiditis(HT) and Rheumatoid arthritis(RA) as well as to explore their effect on eNOS mRNA expression and nitrate production(NOx). Kuwaitis (n = 383) matched by age, gender and ethnicity were genotyped by fluorescent-labelled-restriction fragment length polymorphism (RFLP) and fragment analysis. Expression of eNOS mRNA was analysed using RT-PCR and sera from subjects were screened for NOx using ELISA. Analysis of the allelic frequency revealed a significant association of the 4b allele with susceptibility to SLE (p = 0.0092, OR = 1.76). The 4bb genotype was found to be associated with SLE (p = 0.0076, OR = 1.97) and HT (p = 0.05, OR = 1.81). Allelic and genotypic distribution did not differ between RA patients and healthy control subjects. The 4bb genotype resulted in reduced expression of eNOS mRNA in SLE, RA and HT, but only the reduction in HT was significant (p = 0.05). The 4ab genotype revealed a significant association with increased eNOS expression in HT (p = 0.03) and RA (p = 0.014) patients, and elevated NOx levels were detected in the autoimmune disease cohorts (p < 0.05) when compared to healthy control subjects. The T-786C SNP failed to show a significant association (p > 0.05) with SLE, HT, and RA patients. This study is the first to reveal a significant association between the 4bb genotype of the 27 bp VNTR and susceptibility to HT. The expression of eNOS is related to the number of 27 bp repeats, with heterozygous 4bb repeats showing a decrease in eNOS expression. eNOS – endothelial nitric oxide synthase.

中文翻译：

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内皮型一氧化氮合酶基因内含子4 27bp重复多态性对其在自身免疫性疾病中表达的影响。

本研究的目的是分析 T-786C 多态性和内含子 4 27 bp 可变数串联重复序列 (VNTR) eNOS 标记与系统性红斑狼疮 (SLE)、桥本甲状腺炎 (HT) 和类风湿性关节炎的潜在关联的影响(RA) 以及探索它们对 eNOS mRNA 表达和硝酸盐产生 (NOx) 的影响。通过荧光标记限制性片段长度多态性 (RFLP) 和片段分析对年龄、性别和种族匹配的科威特人 ( n = 383) 进行基因分型。使用 RT-PCR 分析 eNOS mRNA 的表达，并使用 ELISA 筛选受试者血清中的 NOx。等位基因频率分析显示 4b 等位基因与 SLE 易感性显着相关（p = 0.0092 , OR = 1.76 ））。发现 4bb 基因型与 SLE ( p = 0.0076 , OR = 1.97 ) 和 HT ( p = 0.05 , OR = 1.81 ) 相关。等位基因和基因型分布在 RA 患者和健康对照受试者之间没有差异。4bb 基因型导致 SLE、RA 和 HT 中 eNOS mRNA 的表达降低，但只有 HT 的降低是显着的（p = 0.05）。4ab 基因型揭示了与 HT ( p = 0.03) 和 RA ( p = 0.014) 患者中eNOS 表达增加的显着关联，并且在自身免疫性疾病队列中检测到 NOx 水平升高（p< 0.05) 与健康对照受试者相比。T-786C SNP 未能显示出与 SLE、HT 和 RA 患者的显着关联 ( p > 0.05)。这项研究首次揭示了 27 bp VNTR 的 4bb 基因型与 HT 易感性之间的显着关联。eNOS 的表达与 27 bp 重复的数量有关，杂合的 4bb 重复显示 eNOS 表达降低。eNOS——内皮型一氧化氮合酶。