Queensland Institute of Medical Research and Australian Centre for Vaccine Development, 300 Herston Road, Herston, QLD 4006, Australia.
Malar J. 2010 Oct 29;9:302. doi: 10.1186/1475-2875-9-302.
Severe malaria (SM) syndromes caused by Plasmodium falciparum infection result in major morbidity and mortality each year. However, only a fraction of P. falciparum infections develop into SM, implicating host genetic factors as important determinants of disease outcome. Previous studies indicate that tumour necrosis factor (TNF) and lymphotoxin alpha (LTα) may be important for the development of cerebral malaria (CM) and other SM syndromes.
An extensive analysis was conducted of single nucleotide polymorphisms (SNPs) in the TNF, LTA and LTB genes in highland Papuan children and adults, a population historically unexposed to malaria that has migrated to a malaria endemic region. Generated P-values for SNPs spanning the LTA/TNF/LTB locus were corrected for multiple testing of all the SNPs and haplotype blocks within the region tested through 10,000 permutations. A global P-value of < 0.05 was considered statistically significant.
No associations between SNPs in the TNF/LTA/LTB locus and susceptibility to SM in highland Papuan children and adults were found.
These results support the notion that unique selective pressure on the TNF/LTA/LTB locus in different populations has influenced the contribution of the gene products from this region to SM susceptibility.
由恶性疟原虫感染引起的严重疟疾（SM）综合征每年都会导致严重的发病率和死亡率。然而，只有一部分恶性疟原虫感染会发展成 SM，这表明宿主遗传因素是疾病结局的重要决定因素。先前的研究表明，肿瘤坏死因子（TNF）和淋巴毒素α（LTα）可能对脑型疟疾（CM）和其他 SM 综合征的发展很重要。
对高地巴布亚儿童和成人 TNF、LTA 和 LTB 基因中的单核苷酸多态性（SNP）进行了广泛分析，这些儿童和成人生活在一个历史上没有疟疾的高地地区，后来迁移到疟疾流行地区。对跨越 LTA/TNF/LTB 基因座的 SNP 进行了生成的 P 值校正，对该区域内的所有 SNP 和单倍型块进行了多次检验，通过 10000 次随机排列进行校正。P 值<0.05 被认为具有统计学意义。
未发现 TNF/LTA/LTB 基因座中的 SNP 与高地巴布亚儿童和成人对 SM 的易感性之间存在关联。
这些结果支持这样一种观点，即不同人群中对 TNF/LTA/LTB 基因座的独特选择压力影响了该区域基因产物对 SM 易感性的贡献。
