在尼日利亚贝宁城，镰状细胞贫血和血红蛋白 AA 儿童中二氢叶酸还原酶基因突变的独特模式和流行率：HbAA 的影响。

Distinct pattern and prevalence of dihydropteroate synthase gene mutations in children with sickle cell anaemia and haemoglobin AA in Benin City, Nigeria: the impact of HbAA.

机构信息

Edo State University, Uzairue, Edo State, Nigeria.

Institute of Child Health, University of Benin, Benin City, Edo State, Nigeria.

出版信息

Pan Afr Med J. 2022 Oct 13;43:80. doi: 10.11604/pamj.2022.43.80.34334. eCollection 2022.

DOI:10.11604/pamj.2022.43.80.34334

PMID:36590995

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9789784/

Abstract

INTRODUCTION

specific mutations on the Plasmodium falciparum dihydropteroate synthase (Pfdhps) gene mediate sulphadoxine/pyrimethamine (SP) resistance and thus, pose a threat to the efficacy of SP-Intermittent Preventive Therapy (SP-IPT) in malaria chemoprevention in children, including those with sickle cell anaemia (SCA). This study determined the distinct pattern and prevalence of Pfdhps mutations in children with SCA and in those with homozygous haemoglobin A (HbAA) in Benin City, Nigeria; showing the impact of haemoglobin phenotype.

METHODS

this was a cross-sectional study involving children with SCA and HbAA. Those with successfully amplified Pfdhps genes were included in the study. Point mutations and mutant haplotypes of the Pfdhps gene were identified. Parasite density (PD) was determined by estimating the parasite numbers/μl of blood from the thick film. Descriptive, univariable and multivariable analysis were used appropriately.

RESULTS

a total of 146 children: 71 with SCA and 75 with HbAA were recruited, with a mean age of 46.6 ± 13.0 and 36.4 ± 17.6 respectively; proportion of males were 45(63.4%) and 43(57.3%) respectively. I431V, S436A, A437G, A581G, and A613G mutations were present; but the K540E mutation was absent. ISGKAA 41(28.1%) and VAGKGS 61(41.8%) were the most prevalent mutant haplotypes in this study. The prevalence of VAGKGS haplotype 43(57.3%) was significantly higher in HbAA group compared to that 18(25.4%) in the SCA group (p < 0.001). The prevalence of ISGKAA in SCA group 25(35.2%) was significantly higher than that 16(21.3%) in the HbAA group (p=0.032). HbAA phenotype was the only significant predictor for the presence of the VAGKGS mutant haplotype (aOR: 3.0, 95%CI: 1.375 to 6.499; p=0.006).

CONCLUSION

the HbAA phenotype was a significant predictor for the occurrence of the quintuple mutant haplotype (VAGKGS). The K540E mutation was absent; thus, SP-IPT can be explored in children younger than five years with SCA.

摘要

简介

恶性疟原虫二氢叶酸合成酶（Pfdhps）基因的特定突变介导磺胺多辛/乙胺嘧啶（SP）耐药性，从而对儿童疟疾化学预防中的 SP 间歇性预防治疗（SP-IPT）的疗效构成威胁，包括镰状细胞贫血（SCA）儿童。本研究确定了在尼日利亚贝宁城患有 SCA 和纯合血红蛋白 A（HbAA）的儿童中 Pfdhps 基因突变的独特模式和流行率；表明了血红蛋白表型的影响。

方法

这是一项涉及 SCA 和 HbAA 儿童的横断面研究。成功扩增 Pfdhps 基因的儿童被纳入研究。确定 Pfdhps 基因的点突变和突变单倍型。通过估计厚涂片上的血液寄生虫数量/μl 来确定寄生虫密度（PD）。适当使用描述性、单变量和多变量分析。

结果

共招募了 146 名儿童：71 名患有 SCA 和 75 名患有 HbAA，平均年龄分别为 46.6 ± 13.0 和 36.4 ± 17.6；男性比例分别为 45（63.4%）和 43（57.3%）。存在 I431V、S436A、A437G、A581G 和 A613G 突变；但不存在 K540E 突变。ISGKAA 41（28.1%）和 VAGKGS 61（41.8%）是本研究中最常见的突变单倍型。与 SCA 组的 18（25.4%）相比，HbAA 组中 VAGKGS 单倍型 43（57.3%）的流行率显着更高（p < 0.001）。SCA 组中 ISGKAA 的流行率 25（35.2%）显着高于 HbAA 组的 16（21.3%）（p=0.032）。HbAA 表型是存在 VAGKGS 突变单倍型的唯一显着预测因素（优势比：3.0，95%CI：1.375 至 6.499；p=0.006）。