Unité d'Immunogénétique, Institut Pasteur de Dakar, Dakar, Senegal.
Aix Marseille Univ, INSERM, TAGC, MarMaRa Institute, Marseille, France.
Malar J. 2023 Feb 27;22(1):68. doi: 10.1186/s12936-023-04503-8.
Genome-wide association studies have identified ATP2B4 as a severe malaria resistance gene. Recently, 8 potential causal regulatory variants have been shown to be associated with severe malaria.
Genotyping of rs10900585, rs11240734, rs1541252, rs1541253, rs1541254, rs1541255, rs10751450, rs10751451 and rs10751452 was performed in 154 unrelated individuals (79 controls and 75 mild malaria patients). rs10751450, rs10751451 and rs10751452 were genotyped by Taqman assays, whereas the fragment of the ATP2B4 gene containing the remaining SNPs was sequenced. Logistic regression analysis was used to assess the association between the SNPs and mild malaria.
The results showed that mild malaria was associated with rs10900585, rs11240734, rs1541252, rs1541253, rs1541254, rs1541255, rs10751450, rs10751451 and rs10751452. The homozygous genotypes for the major alleles were associated with an increased risk of mild malaria. Furthermore, the haplotype containing the major alleles and that containing the minor alleles were the most frequent haplotypes. Individuals with the major haplotypes had a significantly higher risk of mild malaria compared to the carriers of the minor allele haplotype.
ATP2B4 polymorphisms that have been associated with severe malaria are also associated with mild malaria.
全基因组关联研究已经确定 ATP2B4 是严重疟疾的抗性基因。最近，有 8 个潜在的因果调节变异与严重疟疾有关。
对 154 个无关个体（79 个对照和 75 个轻度疟疾患者）进行 rs10900585、rs11240734、rs1541252、rs1541253、rs1541254、rs1541255、rs10751450、rs10751451 和 rs10751452 的基因分型。rs10751450、rs10751451 和 rs10751452 采用 Taqman 检测进行基因分型，而包含其余 SNPs 的 ATP2B4 基因片段则进行测序。采用逻辑回归分析评估 SNP 与轻度疟疾之间的关联。
结果表明，轻度疟疾与 rs10900585、rs11240734、rs1541252、rs1541253、rs1541254、rs1541255、rs10751450、rs10751451 和 rs10751452 相关。主要等位基因的纯合基因型与轻度疟疾的风险增加相关。此外，包含主要等位基因和次要等位基因的单倍型是最常见的单倍型。与携带次要等位基因单倍型的个体相比，携带主要单倍型的个体患轻度疟疾的风险显著增加。
与严重疟疾相关的 ATP2B4 多态性也与轻度疟疾相关。
