Sickle Cell Foundation Nigeria, Surulere, Lagos, Nigeria.
School of Cancer and Pharmaceutical Sciences, King's College London, London, UK.
J Clin Lab Anal. 2021 Jun;35(6):e23802. doi: 10.1002/jcla.23802. Epub 2021 May 3.
Stroke is a devastating complication of sickle cell anemia (SCA) and can be predicted through abnormally high cerebral blood flow velocity using transcranial Doppler Ultrasonography (TCD). The evidence on the role of alpha-thalassemia and glucose-6-phosphate dehydrogenase (G6PD) deficiency in the development of stroke in children with SCA is conflicting. Thus, this study investigated the association of alpha-thalassemia and G6PD(A ) variant with abnormal TCD velocities among Nigerian children with SCA.
One hundred and forty-one children with SCA were recruited: 72 children presented with normal TCD (defined as the time-averaged mean of the maximum velocity: < 170 cm/s) and 69 children with abnormal TCD (TAMMV ≥ 200 cm/s). Alpha-thalassemia (the α-3.7 globin gene deletion) was determined by multiplex gap-PCR, while G6PD polymorphisms (202G > A and 376A > G) were genotyped using restriction fragment length polymorphism-polymerase chain reaction.
The frequency of α-thalassemia trait in the children with normal TCD was higher than those with abnormal TCD: 38/72 (52.8%) [α-/ α α: 41.7%, α -/ α -: 11.1%] versus 21/69 (30.4%) [α-/ α α: 27.5%, α -/ α -: 2.9%], and the odds of abnormal TCD were reduced in the presence of the α-thalassemia trait [Odds Ratio: 0.39, 95% confidence interval: 0.20-0.78, p = 0.007]. However, the frequencies of G6PDA variant in children with abnormal and normal TCD were similar (11.6% vs. 15.3%, p = 0.522).
Our study reveals the protective role of α-thalassemia against the risk of abnormal TCD in Nigerian children with SCA.
中风是镰状细胞贫血症（SCA）的一种严重并发症，可以通过经颅多普勒超声（TCD）检测到异常高的脑血流速度来预测。关于α-地中海贫血和葡萄糖-6-磷酸脱氢酶（G6PD）缺乏在 SCA 患儿中风发展中的作用的证据存在争议。因此，本研究调查了尼日利亚 SCA 患儿中α-地中海贫血和 G6PD（A）变体与异常 TCD 速度之间的关系。
招募了 141 名 SCA 患儿：72 名患儿 TCD 正常（定义为平均最大速度：<170cm/s），69 名患儿 TCD 异常（TAMMV≥200cm/s）。通过多重缺口聚合酶链反应确定α-地中海贫血（α-3.7 珠蛋白基因缺失），而 G6PD 多态性（202G>A 和 376A>G）则通过限制性片段长度多态性-聚合酶链反应进行基因分型。
TCD 正常的患儿中α-地中海贫血表型的频率高于 TCD 异常的患儿：38/72（52.8%）[α-/αα：41.7%，α-/α-：11.1%]与 21/69（30.4%）[α-/αα：27.5%，α-/α-：2.9%]，并且存在α-地中海贫血表型时 TCD 异常的可能性降低[比值比：0.39，95%置信区间：0.20-0.78，p=0.007]。然而，TCD 异常和正常的患儿中 G6PDA 变体的频率相似（11.6%vs.15.3%，p=0.522）。
本研究揭示了α-地中海贫血对尼日利亚 SCA 患儿异常 TCD 风险的保护作用。
