A study of the TNF/LTA/LTB locus and susceptibility to severe malaria in highland papuan children and adults

作者：Randall Louise M; Kenangalem Enny; Lampah Daniel A; Tjitra Emiliana; Mwaikambo Esther D; Handojo Tjandra; Piera Kim A; Zhao Zhen Z; Rivera Fabian de Labastida; Zhou Yonghong; McSweeney Karli M; Le Lien; Amante Fiona H; Haque Ashraful; Stanley Amanda C; Woodberry Tonia; Salwati Ervi; Granger Donald L; Hobbs Maurine R; Price Ric N; Weinberg J Brice; Montgomery Grant W; Anstey Nicholas M; Engwerda Christian R^*

来源：Malaria Journal, 2010, 9: 302.

DOI：10.1186/1475-2875-9-302

Background: 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 (LT alpha) may be important for the development of cerebral malaria (CM) and other SM syndromes.
Methods: 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.
Results: No associations between SNPs in the TNF/LTA/LTB locus and susceptibility to SM in highland Papuan children and adults were found.
Conclusions: 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.

• 出版日期2010-10-29
• 单位河北医科大学