Identification of a haplotype block in the 5q31 cytokine gene cluster associated with the susceptibility to severe malaria
Identification of a haplotype block in the 5q31 cytokine gene cluster associated with the susceptibility to severe malaria
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DOI：
10.1186/1475-2875-8-232
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发表时间：
2009-10-19
期刊：
影响因子：
3
通讯作者：
Ohashi, Jun
中科院分区：
文献类型：
--
作者：
Naka, Izumi;Nishida, Nao;Ohashi, Jun
背景资料：先前已经证明，IL 13启动子区域中的单核苷酸多态性（SNP），IL 13 - 1055 T>C（rs 1800925），与泰国人对严重疟疾的易感性相关。在本研究中，使用相同的疟疾受试者对染色体5 q31上的细胞因子基因簇（包括IL 4、IL 5和IL 13）进行精细关联作图，以细化包含对严重疟疾易感的主要变体或单倍型的区域。对368例恶性疟原虫疟疾患者5 q31区522 kb的82个SNPs进行了分析（203名轻度疟疾患者和165名重度疟疾患者）。只有rs 1881457位于IL 13的启动子区，与rs 1800925连锁不平衡（r（2）= 0.73），在调整多重检验后，显示与严重疟疾显著相关（排列检验P = 0.046）。该SNP位于一个跨度为97 kb的单倍型区块中（从rs 2069812到rs 2240032）。检测到的单倍型块包含RAD 50基因和IL 13的启动子，但没有其他的genes.Conclusion：一个单倍型块，其中一个主要的多态性与严重的疟疾是可能被编码在泰国疟疾患者。
Background: It has been previously demonstrated that a single nucleotide polymorphism (SNP) in the IL13 promoter region, IL13 -1055T>C (rs1800925), was associated with susceptibility to severe malaria in Thais. In the present study, fine association mapping for a cytokine gene cluster including IL4, IL5, and IL13 on chromosome 5q31 was conducted using the same malaria subjects to refine the region containing a primary variant or a haplotype susceptible to severe malaria.Methods: A total of 82 SNPs spanning 522 kb of the 5q31 region were analysed in 368 patients with Plasmodium falciparum malaria (203 mild malaria and 165 severe malaria patients).Results: Only rs1881457 located in the promoter region of IL13, which is in linkage disequilibrium with rs1800925 (r(2) = 0.73), showed a significant association with severe malaria after adjusting for multiple testing (P = 0.046 by permutation test). This SNP was in a haplotype block spanning 97 kb (from rs2069812 to rs2240032). The detected haplotype block contained the RAD50 gene and the promoter of IL13, but not the other genes.Conclusion: A haplotype block in which a primary polymorphism associated with severe malaria is likely to be encoded was identified in Thai malaria patients.