斯里兰卡选定人群中宿主遗传多态性与疟疾血清学反应的关系。

Host genetic polymorphisms and serological response against malaria in a selected population in Sri Lanka.

机构信息

Department of Parasitology, Faculty of Medicine, University of Colombo, Kynsey Road, Colombo 8, Sri Lanka.

Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.

出版信息

Malar J. 2018 Dec 17;17(1):473. doi: 10.1186/s12936-018-2622-9.

DOI:10.1186/s12936-018-2622-9

PMID:30558622

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6296029/

Abstract

BACKGROUND

Antibodies against the merozoite surface protein 1 (MSP1) and the apical membrane antigen 1 (AMA1) of the malaria parasite (Plasmodium vivax) are proven to be important in protection against clinical disease. Differences in the production/maintenance of antibodies may be due to many factors including host genetics. This paper discusses the association of 4 anti-malarial antibodies with selected host genetic markers.

METHODS

Blood was collected from individuals (n = 242) with a history of malaria within past 15 years for DNA and serum. ELISA was carried out for serum to determine the concentration of anti-malarial antibodies MSP1 and AMA1 for both vivax and falciparum malaria. 170 SNPs related to malaria were genotyped. Associations between seropositivity, antibody levels and genetic, non-genetic factors were determined.

RESULTS

Age ranged 13-74 years (mean age = 40.21 years). Majority were females. Over 90% individuals possessed either one or more type(s) of anti-malarial antibodies. Five SNPs were significantly associated with seropositivity. One SNP was associated with MSP1_Pv(rs739718); 4 SNPs with MSP1_Pf (rs6874639, rs2706379, rs2706381 and rs2075820) and1 with AMA1_Pv (rs2075820). Eleven and 7 genotypes (out of 15) were significantly associated with either presence or absence of antibodies. Three SNPs were found to be significantly associated with the antibody levels viz. rs17411697 with MSP1_Pv, rs2227491 with AMA1_Pv and rs229587 with AMA1_Pf. Linkage of the markers in the two groups was similar, but lower LOD scores were observed in seropositives compared to seronegatives.

DISCUSSION AND CONCLUSIONS

The study suggests that several SNPs in the human genome that exist in Sri Lankan populations are significantly associated with anti-malarial antibodies, either with generation and/or maintenance of antibodies for longer periods, which can be due to either individual polymorphisms or most probably a combined effect of the markers.

摘要

背景

针对疟原虫（间日疟原虫）裂殖子表面蛋白 1（MSP1）和顶膜抗原 1（AMA1）的抗体已被证明对预防临床疾病具有重要作用。抗体的产生/维持差异可能是由于多种因素引起的，包括宿主遗传因素。本文讨论了与选定宿主遗传标记相关的 4 种抗疟抗体。

方法

从过去 15 年内有疟疾病史的个体（n=242）中采集血液，用于 DNA 和血清。通过 ELISA 法测定血清中针对间日疟原虫和恶性疟原虫的 MSP1 和 AMA1 抗疟抗体浓度。对与疟疾相关的 170 个 SNP 进行基因分型。确定血清阳性、抗体水平与遗传和非遗传因素之间的关系。

结果

年龄在 13-74 岁之间（平均年龄为 40.21 岁），大多数为女性。超过 90%的个体具有一种或多种抗疟抗体。有 5 个 SNP 与血清阳性显著相关。一个 SNP 与 MSP1_Pv(rs739718)相关；4 个 SNP 与 MSP1_Pf(rs6874639、rs2706379、rs2706381 和 rs2075820)相关，1 个 SNP 与 AMA1_Pv(rs2075820)相关。11 个基因型（15 个中的 7 个）与抗体的存在或不存在显著相关。发现 3 个 SNP 与抗体水平显著相关，即 rs17411697 与 MSP1_Pv、rs2227491 与 AMA1_Pv 和 rs229587 与 AMA1_Pf。在两组中，标记的连锁相似，但与血清阴性者相比，血清阳性者的 LOD 评分较低。