The impaired bioavailability of endogenous nitric oxide (NO) in sickle cell anemia (SCA) may be influenced by polymorphisms in the endothelial nitric oxide synthase gene (eNOS). We compared allelic/genotypic frequencies of the eNOS polymorphisms T-786C, VNTR4a/b and G894T between 89 adult SCA patients and 100 healthy controls, and investigated the relationship between these SNPs and markers of hemolysis [lactate dehydrogenase (LDH), indirect bilirubin (IB) and reticulocyte counts], inflammation [interleukins IL-1β, IL-6, IL-8, Tumor Necrosis Factor (TNF-α) and C-reactive protein (CRP)] and endothelial dysfunction (ED) [soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), soluble L-selectin (sL-selectin), von Willebrand Factor (vWF) antigen and D-dimers] in the patients. The frequencies of the mutant -786C allele and -786C/C genotype were significantly higher in patients (p = 0.02 and p = 0.04, respectively) but not significantly correlated with the markers. For VNTR4a/b and G894T, the allelic/genotypic frequencies did not statistically differ between patient and control groups. Patients carrying the 4a allele and those with the 894G/G genotype showed a significant decrease in IB (p = 0.02 and p = 0.04, respectively), and only patients with the 4a allele exhibited reduced IL-1β (p = 0.01). The correlation profiles between markers of inflammation and ED significantly differed between patients carrying the mutant alleles and those with wild-type genotypes. This appears to be the first report on the relationship between eNOS gene polymorphisms and markers of hemolysis, inflammation and ED in Brazilian SCA patients. Our results indicate that the SNPs analyzed may influence the phenotypic variability of these patients.

中文翻译：

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巴西镰状细胞性贫血患者的内皮型一氧化氮合酶（eNOS）基因多态性和溶血，炎症和内皮功能障碍的标志物。

镰状细胞性贫血（SCA）中内源性一氧化氮（NO）的生物利用度受损可能受到内皮型一氧化氮合酶基因（eNOS）多态性的影响。我们比较了eNOS的等位基因/基因型频率多态性T-786C，VNTR4a / b和G894T多态性在89位成人SCA患者和100位健康对照之间进行，并研究了这些SNP与溶血标志物[乳酸脱氢酶（LDH），间接胆红素（IB）和网织红细胞计数]，炎症[白介素IL-1β，IL-6，IL-8，肿瘤坏死因子（TNF-α）和C反应蛋白（CRP）]和内皮功能障碍（ED）[可溶性血管细胞粘附分子-1（sVCAM-1），可溶性细胞间粘附分子-1（sICAM-1），可溶性L-选择素（sL-selectin），von Willebrand因子（vWF）抗原和D-二聚体]。突变体的频率- 786C等位基因和-786C / C基因型分别为患者（显著更高p  = 0.02和p =分别为0.04），但与标记没有显着相关。对于VNTR4a / b和G894T，患者和对照组之间的等位基因/基因型频率无统计学差异。携带4a等位基因的患者和894G / G基因型患者的IB显着降低（分别为p  = 0.02和p  = 0.04），只有患有4a等位基因的患者的IL-1β降低（p  = 0.01）。在携带突变等位基因的患者和具有野生型基因型的患者之间，炎症标志物和ED的相关性差异显着。这似乎是有关eNOS之间关系的第一份报告基因的多态性和溶血，炎症和ED在巴西SCA患者中的标记。我们的结果表明，所分析的SNP可能影响这些患者的表型变异性。