背景:全基因组关联研究已经确定ATP2B4是一种严重的疟疾抗性基因。最近,8个潜在的因果调节变异已被证明与严重疟疾有关。
方法:在154名无关个体(79名对照和75名轻度疟疾患者)中对rs10900585、rs11240734、rs1541252、rs1541253、rs1541254、rs1541255、rs10751450、rs10751451和rs10751452进行基因分型。rs10751450,rs10751451和rs10751452通过Taqman分析进行基因分型,而包含剩余SNP的ATP2B4基因片段被测序。使用Logistic回归分析评估SNP与轻度疟疾之间的相关性。
结果:结果显示轻度疟疾与rs10900585,rs11240734,rs1541252,rs1541253,rs1541254,rs1541255,rs10751450,rs10751451和rs10751452有关。主要等位基因的纯合基因型与轻度疟疾的风险增加有关。此外,含有主要等位基因的单倍型和含有次要等位基因的单倍型是最常见的单倍型。与次要等位基因单倍型的携带者相比,具有主要单倍型的个体患轻度疟疾的风险明显更高。
结论:与重度疟疾相关的ATP2B4多态性也与轻度疟疾相关。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: ATP2B4 polymorphisms that have been associated with severe malaria are also associated with mild malaria.