Meher Satyabrata, Mohanty Pradeep K, Patel Siris, Das Kishalaya, Sahoo Sarmila, Dehury Snehadhini, Mohapatra Manoj K, Jit Bimal P, Das Padmalaya, Dash Bisnu P
Odisha Sickle Cell Project (NHM), Sickle Cell Clinic and Molecular Biology Laboratory, Veer Surendra Sai Institute of Medical Science & Research (VIMSAR), Burla, Sambalpur, Odisha, India.
Department of Bioscience and Biotechnology, Fakir Mohan University, Balasore, Odisha, India.
Hemoglobin. 2021 Nov;45(6):358-364. doi: 10.1080/03630269.2020.1801459. Epub 2021 Jan 3.
Sickle cell anemia is hallmarked by hemolysis, which releases hemoglobin (Hb) into the plasma promoting vaso-occlusive crisis (VOC). Haptoglobin (Hp) clears free Hb and decreases Hb-related pathophysiology in sickle cell anemia. There are two alleles (HP1 and HP2) and three genotypes (HP1-1, HP1-2 and HP2-2) of Hp with different frequencies in different populations. This study involved Hp level and genotype among normal and sickle cell anemia patients with varying severity of VOC. A total of 297 sickle cell anemia patients and 98 healthy controls were selected for the study. The sickle cell anemia patients were categorized as 'mild-phenotype' with no pain episodes and 'severe-phenotype' as having three or more acute pain episodes in the preceding 12 months. The Hp level was significantly lower ( < 0.001) in sickle cell patients anemia than controls; HP1-1 genotype had a higher Hp level compared to HP1-2 and HP2-2 ( < 0.05). Turkey-Kramer multiple comparison tests showed that mild and severe phenotypes have significant differences ( < 0.05) in Hb F%, Hb, platelet count, aspartate aminotransferase (AST), alanine aminotransferase (ALT), direct-bilirubin (Bil-D), total-bilirubin (Bil-T), lactate dehydrogenase (LDH) and Hp level. Pearson correlation revealed that Hp level has a positive ( < 0.05) correlation with Hb F%, Hb, packed cell volume (PCV) and serum urea; in contrast its level is negatively correlated with AST, ALT, Bil-T and LDH. A significantly higher frequency of HP2 allele and HP2-2 genotypes was found in severe phenotypes. In the studied population, it was found that higher HP2 frequency, low Hp level and more hemolysis favors the onset of VOC in sickle cell anemia.
镰状细胞贫血的特征是溶血，溶血会将血红蛋白（Hb）释放到血浆中，从而引发血管闭塞性危机（VOC）。结合珠蛋白（Hp）可清除游离Hb，并减轻镰状细胞贫血中与Hb相关的病理生理过程。Hp有两个等位基因（HP1和HP2）和三种基因型（HP1-1、HP1-2和HP2-2），在不同人群中的频率不同。本研究涉及正常人和患有不同严重程度VOC的镰状细胞贫血患者的Hp水平和基因型。共选择了297例镰状细胞贫血患者和98例健康对照进行研究。镰状细胞贫血患者被分为无疼痛发作的“轻度表型”和在过去12个月中有三次或更多次急性疼痛发作的“重度表型”。镰状细胞贫血患者的Hp水平显著低于对照组（<0.001）；与HP1-2和HP2-2相比，HP1-1基因型的Hp水平更高（<0.05）。Turkey-Kramer多重比较检验显示，轻度和重度表型在Hb F%、Hb、血小板计数、天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、直接胆红素（Bil-D）、总胆红素（Bil-T）、乳酸脱氢酶（LDH）和Hp水平上有显著差异（<0.05）。Pearson相关性分析显示，Hp水平与Hb F%、Hb、红细胞压积（PCV）和血清尿素呈正相关（<0.05）；相反，其水平与AST、ALT、Bil-T和LDH呈负相关。在重度表型中发现HP2等位基因和HP2-2基因型的频率显著更高。在研究人群中，发现较高的HP2频率、较低的Hp水平和更多的溶血有利于镰状细胞贫血中VOC的发作。
