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乌干达伊甘加地区触珠蛋白基因多样性与儿童无并发症疟疾发病情况。

Haptoglobin gene diversity and incidence of uncomplicated malaria among children in Iganga, Uganda.

机构信息

School of Biomedical Sciences, College of Health Sciences, Makerere University, PO Box 7072, Kampala, Uganda.

Department of Biochemistry, Uganda Christian University School of Medicine, PO BOX 4, Mukono, Uganda.

出版信息

Malar J. 2020 Nov 26;19(1):435. doi: 10.1186/s12936-020-03515-y.

DOI:10.1186/s12936-020-03515-y
PMID:33243242
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7690179/
Abstract

BACKGROUND

Haptoglobin (Hp) is an acute phase protein that takes part in systemic regulation of haem during Plasmodium falciparum infections. Numerous genotypes of haptoglobin have been reported in malaria endemic populations. In this study, the relationship between haptoglobin genotypes and incidence of uncomplicated malaria in a cohort of children living in a malaria-endemic area of Uganda was determined.

METHODS

This is an extension of a longitudinal study comprising of 423 children aged between six months and nine years, who were actively followed up for one year. Malaria episodes occurring in the cohort children were detected and the affected children treated with national policy drug regimen. Haptoglobin genotypes were determined by an allele-specific PCR method and their frequencies were calculated. A multivariate negative binomial regression model was used to estimate the impact of haptoglobin genotypes on incidence of uncomplicated malaria in the children's cohort. In all statistical tests, a P-value of < 0.05 was considered as significant.

RESULTS

The prevalence of the Hp 1-1, Hp 2-1 and Hp 2-2 genotypes in the children's cohort was 41%, 36.2% and 22.9%, respectively. The overall frequency for the Hp 1 allele was 59%, while Hp 2 allele occurred at a frequency of 41%. After adjustment of incidence rates for age, insecticide treated bed net (ITN) use and malaria history, the incidence of uncomplicated malaria for children carrying the Hp 2-2 genotype and those with the Hp 2-1 genotype was statistically similar (P = 0.41). Also, no difference in the incidence of uncomplicated malaria was observed between children carrying the Hp 1-1 genotype and those having the Hp 2-1 genotype (P = 0.84) or between Hp 2-2 Vs Hp 1-1 genotypes (P = 0.50).

CONCLUSIONS

This study showed that the Hp 1-1 and Hp 2-1 genotypes each occur in nearly 4 in 10 children and the Hp 2-2 genotype occurs in 2 of every 10 children. No association with incidence of uncomplicated malaria was found. Additional studies of influence of haptoglobin genotypes on P. falciparum malaria severity are needed to understand the role of these genotypes in malarial protection.

摘要

背景

触珠蛋白(Hp)是一种急性期蛋白,参与恶性疟原虫感染期间的系统性血红素调节。在疟疾流行地区已经报道了触珠蛋白的许多基因型。本研究旨在确定在乌干达一个疟疾流行地区的儿童队列中,触珠蛋白基因型与无并发症疟疾发生率之间的关系。

方法

这是一项纵向研究的扩展,该研究包括 423 名 6 个月至 9 岁的儿童,对其进行了为期一年的积极随访。检测队列儿童中发生的疟疾发作,并使用国家政策药物方案对受影响的儿童进行治疗。通过等位基因特异性 PCR 方法确定触珠蛋白基因型,并计算其频率。使用多变量负二项回归模型估计触珠蛋白基因型对儿童队列中无并发症疟疾发生率的影响。在所有统计检验中,P 值<0.05 被认为具有统计学意义。

结果

在儿童队列中,Hp 1-1、Hp 2-1 和 Hp 2-2 基因型的患病率分别为 41%、36.2%和 22.9%。Hp 1 等位基因的总频率为 59%,而 Hp 2 等位基因的频率为 41%。在调整年龄、驱虫蚊帐(ITN)使用和疟疾史的发病率后,携带 Hp 2-2 基因型和 Hp 2-1 基因型的儿童无并发症疟疾的发病率相似(P=0.41)。此外,携带 Hp 1-1 基因型的儿童与携带 Hp 2-1 基因型的儿童(P=0.84)或 Hp 2-2 与 Hp 1-1 基因型的儿童(P=0.50)之间无无并发症疟疾发病率的差异。

结论

本研究表明,Hp 1-1 和 Hp 2-1 基因型在每 10 名儿童中各出现近 4 名,而 Hp 2-2 基因型在每 10 名儿童中出现 2 名。未发现与无并发症疟疾发生率相关。需要进一步研究触珠蛋白基因型对恶性疟原虫疟疾严重程度的影响,以了解这些基因型在疟疾保护中的作用。

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本文引用的文献

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Malar J. 2015 Sep 5;14:341. doi: 10.1186/s12936-015-0875-0.
2
Epistasis between the haptoglobin common variant and α+thalassemia influences risk of severe malaria in Kenyan children.携带血红蛋白常见变异型与α-地中海贫血症之间的上位性作用影响肯尼亚儿童罹患重症疟疾的风险。
Blood. 2014 Mar 27;123(13):2008-16. doi: 10.1182/blood-2013-10-533489. Epub 2014 Jan 29.
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Haptoglobin phenotype prevalence and cytokine profiles during Plasmodium falciparum infection in Dogon and Fulani ethnic groups living in Mali.在马里生活的多贡族和富拉尼族中,疟原虫感染期间触珠蛋白表型流行情况和细胞因子谱。
Malar J. 2013 Nov 25;12:432. doi: 10.1186/1475-2875-12-432.
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Mechanisms of haptoglobin protection against hemoglobin peroxidation triggered endothelial damage.触珠蛋白防止血红蛋白过氧化引发内皮损伤的机制。
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Acta Trop. 2013 May;126(2):127-31. doi: 10.1016/j.actatropica.2013.02.004. Epub 2013 Feb 13.
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