アンゴラの小児患者コホートにおけるα-タラセミアと鎌状赤血球症の共遺伝

Co-Inheritance of alpha-thalassemia and sickle cell disease in a cohort of Angolan pediatric patients.

• Brígida Santos
• Mariana Delgadinho
• Joana Ferreira
• Isabel Germano
• Armandina Miranda
• Ana Paula Arez
• Paula Faustino
• Miguel Brito

抄録

本研究の目的は、アンゴラの鎌状赤血球症小児患者におけるα-タラセミア、胎児ヘモグロビン、血液学的指標、臨床的有害事象との関連を探ることであった。ルアンダとカキシートで合計 200 人の鎌状赤血球症（SCD）小児を採取した。静脈血液サンプルを採取し、血液学的分析、胎児ヘモグロビン定量、GAP-PCRによる3.7 kb α-タラセミア欠失の遺伝子型決定に使用した。3.7kbのα-タラセミア欠失のホモ接合性における頻度は12.5%、ヘテロ接合性における頻度は55.0%であった。5歳以上の小児ではα-タラセミア頻度の増加が認められた（11.7％対13.00％）。さらに、3.7kbのα-タラセミア欠失ホモ接合体では、最初の発現年齢が有意に高く、年別輸血回数が少なく、ヘモグロビンが高く、平均冠血量、平均冠血ヘモグロビンが低く、網状細胞数の減少により観察される溶血率が低かった。胎児ヘモグロビンについては、3つの遺伝子型間で差は認められなかった。さらに、α-タラセミアを共遺伝させた場合、脳卒中イベント、骨髄炎、脾腫、脾摘出、肝腫の発生数が低かった。アンゴラ人集団において初めて、鎌状赤血球症におけるα-タラセミア欠失の影響を解析した結果、α-タラセミアは血液学的・臨床的側面に影響を与え、よりマイルドな表現型をもたらすことが明らかになった。

The aim of this study was to explore the association between alpha-thalassemia, fetal hemoglobin, hematological indices, and clinical adverse events in Angolan sickle cell disease pediatric patients. A total of 200 sickle cell disease (SCD) children were sampled in Luanda and Caxito. A venous blood sample was collected and used for hematological analyses, fetal hemoglobin quantification, and genotyping of 3.7 kb alpha-thalassemia deletion by GAP-PCR. The frequency of the 3.7 kb alpha-thalassemia deletion in homozygosity was 12.5% and in heterozygosity was 55.0%. An increase in alpha-thalassemia frequency was observed in children older than 5 years old (11.7% vs. 13.00%). Furthermore, 3.7 kb alpha-thalassemia deletion homozygotes had a significantly higher age of the first manifestation, lower number of blood transfusions by year, higher hemoglobin, lower mean corpuscular volume, mean corpuscular hemoglobin, and lower hemolytic rate observed by a lower number of reticulocytes count. There were no differences in fetal hemoglobin between the three genotypes. Moreover, the number of stroke events, osteomyelitis, splenomegaly, splenectomy, and hepatomegaly were lower when alpha-thalassemia was co-inherited. For the first time in Angolan population, the effect of alpha-thalassemia deletion in sickle cell disease was analyzed and results reinforce that this trait influences the hematological and clinical aspects and produces a milder phenotype.