Mansouri A, Nandy I
Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, USA.
J Investig Med. 1998 Feb;46(2):82-6.
Sickle cell trait, glucose-6-phosphate dehydrogenase (G6PD) deficiency and alpha-thalassemia trait are common genetic abnormalities among the American Black population. Under oxidative stress, the presence of any of these conditions would predispose the hemoglobin (Hb) to oxidation resulting in accelerated methemoglobin (metHb) formation. It was hypothesized that red cells phenotypic for these genetic variants should have more or different levels of metHb reductase (cytochrome b5 reductase) activity.
To test this hypothesis, we measured the red cell metHb reductase activity in 558 male subjects (316 Blacks and 242 Whites), by the procedure described by Beutler. All Black patients also had G6PD spot test and Hb electrophoresis. In addition, all patients had a complete blood count (CBC). If the hematocrit was < 35% a reticulocyte count was also done. Patients with corrected reticulocyte (retic count X hematocrit/45) index over 2% were excluded regardless of other findings.
The results showed that Blacks had different metHb reductase activity levels than Whites (mean = 3.19 vs 2.89 IU/gHb, respectively with p = 0.03). However, the differences in metHb reductase activities in patients with sickle cell trait, G6PD deficiency, and low MCV < 80 micron3 (presumptively having alpha-thalassemia) in small subgroups did not reach statistical significance (p = 0.2), although, all 3 groups were comprised of small numbers.
It is concluded that American Blacks have significantly different metHb reductase activity. The different metHb reductase activity in Blacks seems to be unrelated to the presence of G6PD deficiency, sickle cell trait, or alpha-thalassemia and it may be the result of genetic polymorphism. However, our study samples do not exactly represent the cross-sections of the Black and White populations. In addition, all patients were male in this study. Therefore, this study should be confirmed using larger and more population-representative samples. The clinical significance of this problem is not clear at this time.
镰状细胞性状、葡萄糖-6-磷酸脱氢酶（G6PD）缺乏症和α地中海贫血性状是美国黑人人群中常见的遗传异常。在氧化应激下，这些情况中的任何一种都会使血红蛋白（Hb）易于氧化，导致高铁血红蛋白（metHb）形成加速。据推测，具有这些遗传变异表型的红细胞应具有更高或不同水平的高铁血红蛋白还原酶（细胞色素b5还原酶）活性。
为了验证这一假设，我们采用Beutler描述的方法，测量了558名男性受试者（316名黑人，242名白人）的红细胞高铁血红蛋白还原酶活性。所有黑人患者还进行了G6PD斑点试验和血红蛋白电泳。此外，所有患者均进行了全血细胞计数（CBC）。如果血细胞比容<35%，则还进行网织红细胞计数。无论其他检查结果如何，校正网织红细胞（网织红细胞计数×血细胞比容/45）指数超过2%的患者均被排除。
结果显示，黑人的高铁血红蛋白还原酶活性水平与白人不同（平均值分别为3.19 IU/gHb和2.89 IU/gHb，p = 0.03）。然而，在小亚组中，镰状细胞性状、G6PD缺乏症和低平均红细胞体积<80立方微米（推测患有α地中海贫血）患者的高铁血红蛋白还原酶活性差异未达到统计学意义（p = 0.2），尽管这3组的样本量都很小。
得出的结论是，美国黑人的高铁血红蛋白还原酶活性存在显著差异。黑人中不同的高铁血红蛋白还原酶活性似乎与G6PD缺乏症、镰状细胞性状或α地中海贫血的存在无关，可能是基因多态性的结果。然而，我们的研究样本并不完全代表黑人和白人人群的横断面。此外，本研究中的所有患者均为男性。因此，应使用更大且更具人群代表性的样本对本研究进行验证。目前这个问题的临床意义尚不清楚。
