Tetteh Danquah Adjoa, Courtin David, Asamoah Sakyi Samuel, Nakotey Gideon Kwesi, Tchum Samuel Kofi, Afriyie Duah Nana, Lagrave Alisé, Sewor Christian, Amoani Benjamin
Department of Microbiology and Immunology, School of Medical Sciences, University of Cape Coast, Cape Coast, Ghana.
UMR 261 MERIT, Université de Paris, Institut de Recherche pour le Développement (IRD), Paris, France.
PLoS One. 2025 Sep 15;20(9):e0322524. doi: 10.1371/journal.pone.0322524. eCollection 2025.
Malaria is a paramount health concern mostly among infants and young children. The World Health Organization recommends iron fortification for children with iron deficiency anaemia living in malaria-endemic regions like Ghana. However, the intricate interplay between genetic polymorphisms and nutritional interventions in malaria susceptibility and severity remains unclear. The Human Leukocyte Antigen-G (HLA-G) locus within the Major Histocompatibility Complex (MHC) genes has surfaced as a critical player in regulating immune responses and influencing disease outcomes. Therefore, we aimed to evaluate the effect of HLA-G 14 bp polymorphism and its associated risk of malaria severity among Ghanaian infants and young children on iron fortification.
This secondary double-blinded cluster randomized controlled trial involved 432 archival samples from the Tain District and Wenchi Municipal in the Bono Region. Participants aged between 6 and 36 months and consuming semi-solid foods were recruited in the study while children with malaria infection or other known medical conditions were excluded. Capillary blood samples were taken for anaemia determination using a haematology autoanalyzer, malaria infection status, and parasitaemia were assessed via microscopy, and HLA-G 14 bp polymorphism using PCR. Hardy-Weinberg equilibrium and multivariate regression models were used to analyze the data obtained.
The research findings indicate that among the iron-fortified children with HLA-G, 14 bp + /- and 14 bp-/- variants are likely to develop severe malaria. Also, the HLA-G 14 bp + /- variant was linked to a higher risk of anaemia development among participants who received iron supplements.
The study results indicated that iron-fortified individuals carrying the HLA-G 14 bp insertion/deletion polymorphism have an elevated risk of developing severe malaria, which in turn predisposes them to anaemia.
疟疾是主要影响婴幼儿的重大健康问题。世界卫生组织建议，生活在加纳等疟疾流行地区的缺铁性贫血儿童应进行铁强化。然而，基因多态性与营养干预在疟疾易感性和严重程度方面的复杂相互作用仍不明确。主要组织相容性复合体（MHC）基因中的人类白细胞抗原-G（HLA-G）位点已成为调节免疫反应和影响疾病结局的关键因素。因此，我们旨在评估加纳婴幼儿中HLA-G 14 bp多态性及其与疟疾严重程度相关风险对铁强化的影响。
这项二次双盲整群随机对照试验涉及来自博诺地区泰恩区和温奇市的432份存档样本。招募年龄在6至36个月且食用半固体食物的参与者，排除患有疟疾感染或其他已知疾病的儿童。采集毛细血管血样，使用血液学自动分析仪测定贫血情况，通过显微镜评估疟疾感染状况和寄生虫血症，并使用聚合酶链反应检测HLA-G 14 bp多态性。采用哈迪-温伯格平衡和多变量回归模型分析所得数据。
研究结果表明，在接受铁强化的HLA-G儿童中，14 bp + /-和14 bp-/-变异体可能会发展为重症疟疾。此外，HLA-G 14 bp + /-变异体与接受铁补充剂的参与者发生贫血的较高风险相关。
研究结果表明，携带HLA-G 14 bp插入/缺失多态性的铁强化个体患重症疟疾的风险升高，进而易患贫血。
