Department of Infectious Disease Research, Armed Forces Medical Research Institute, 90bun, Jaunro, Yuseong-gu, Daejeon, 34059, Republic of Korea.
Division of Vectors & Parasitic Diseases, Center for Laboratory Control of Infectious Diseases, Korea Centers for Disease Control & Prevention, 187 Osongsaengmyeong 2-ro, Osong-eup, Heungduk-gu, Cheongju-si, Chungbuk, 28159, Republic of Korea.
Malar J. 2020 Sep 1;19(1):317. doi: 10.1186/s12936-020-03393-4.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most prevalent inborn disorder. This X-chromosome-linked recessive disease affects more than 400 million people globally, and is associated with haemolytic anaemia after medication with the anti-latent malaria drug, primaquine. To prevent malaria, the Republic of Korea (ROK) Army administers malaria chemoprophylaxis. Due to the previously low G6PD deficiency prevalence in the ROK, prior to primaquine administration, testing for G6PD deficiency was not mandatory. In this study, to evaluate the risk from malaria chemoprophylaxis in the ROK, G6PD deficiency prevalence was investigated.
Blood specimens from 1632 soldiers entering training camp for the 3 Infantry of the ROK Army were collected. CareStart™ Biosensor for G6PD and haemoglobin (Hb) was used to detect G6PD levels. G6PD variants using the DiaPlexC G6PD Genotyping kit (Asian type) and full-length sequencing were examined.
Of 1632 blood specimens tested, none was observed to be G6PD deficient. The median value of all tested samples was 7.582 U/g Hb. An investigation of 170 G6PD DNA variants was analysed and categorized as partially low normal [n = 131, 30-80% (2.27-6.05 U/g Hb) of the median value], high [n = 3, > 150% (> 11.373 U/g Hb) of the median value], or normal [n = 36, 80-150% (6.05-11.373 U/g Hb) of the median value], and none was amplified by the DiaPlexC kit. Five silent mutations (C→T) in 131 partially low normal specimens were found at the 1311th nucleotide position by sequence analysis. Another 8 silent mutations (T93C) were also detected in 131 partially low normal specimens. Thus, it is inferred that these silent mutations could be related to G6PD activity.
This G6PD deficiency prevalence study, conducted among participants from the 3rd Infantry of the ROK Army, provided crucial evidence for the safety of malaria chemoprophylaxis. This study showed that the prevalence of G6PD deficiency among 1632 young soldiers was wholly absent. Although G6PD phenotypic mutations were not detected, many silent mutations (C1311T and T93C) were observed. Thus, it is inferred that malaria chemoprophylaxis is relatively safe against G6PD deficiency-mediated haemolytic anaemia. However, given the number of individuals whose G6PD were at the partially low normal range and the frequent detection of G6PD deficiency-related mutations, consistent monitoring of G6PD deficiency is needed.
葡萄糖-6-磷酸脱氢酶（G6PD）缺乏症是最常见的遗传性疾病。这种 X 连锁隐性疾病影响着全球超过 4 亿人，在服用抗潜伏疟药物伯氨喹后会导致溶血性贫血。为了预防疟疾，韩国陆军（ROK）军队进行疟疾化学预防。由于 ROK 以前 G6PD 缺乏症的患病率较低，在服用伯氨喹之前，G6PD 缺乏症的检测并非强制性的。在这项研究中，为了评估 ROK 疟疾化学预防的风险，我们调查了 G6PD 缺乏症的患病率。
采集了 1632 名进入 ROK 陆军第三步兵师训练营的士兵的血液标本。使用 CareStart™ Biosensor 进行 G6PD 和血红蛋白（Hb）检测。使用 DiaPlexC G6PD 基因分型试剂盒（亚洲型）和全长测序检测 G6PD 变体。
在 1632 份检测的血样中，没有观察到 G6PD 缺乏症。所有测试样本的中位数值为 7.582 U/g Hb。对 170 个 G6PD DNA 变体的调查和分类为部分低正常[ n = 131，中位数值的 30-80%（2.27-6.05 U/g Hb）]、高[ n = 3，高于中位数值的 150%（>11.373 U/g Hb）]或正常[ n = 36，中位数值的 80-150%（6.05-11.373 U/g Hb）]，并且 DiaPlexC 试剂盒均未扩增。通过序列分析，在 131 个部分低正常标本的第 1311 个核苷酸位置发现了 5 个沉默突变（C→T）。在 131 个部分低正常标本中还检测到了另外 8 个沉默突变（T93C）。因此，可以推断这些沉默突变可能与 G6PD 活性有关。
在 ROK 陆军第三步兵师的参与者中进行的这项 G6PD 缺乏症患病率研究为疟疾化学预防的安全性提供了重要证据。这项研究表明，在 1632 名年轻士兵中，G6PD 缺乏症的患病率完全不存在。虽然没有检测到 G6PD 表型突变，但观察到许多沉默突变（C1311T 和 T93C）。因此，可以推断，疟疾化学预防对 G6PD 缺乏症介导的溶血性贫血相对安全。然而，鉴于部分 G6PD 处于低正常范围的人数众多，以及 G6PD 缺乏相关突变的频繁检测，需要对 G6PD 缺乏症进行持续监测。
