Interleukin-1 gene cluster polymorphisms and susceptibility to clinical malaria in a Gambian case–control study

Abstract

Interleukin-1 (IL1) is a potent endogenous pyrogen and inducer of the acute phase response, and these innate immune responses are an important part of the human host's initial reaction to infection by the malaria parasite. In addition, several single-nucleotide polymorphisms (SNPs) in this region have previously been demonstrated to be associated with susceptibility to infectious disease. Therefore, a possible association with malaria susceptibility was investigated. A total of 13 polymorphic markers were used in a two-stage screening strategy to genotype a Gambian case -control study group by either restriction endonuclease digestion or the Sequenom MassARRAYt assay. This involved an initial screen of 188 severe cases and 188 mild controls, and if there was a significant association with a malaria phenotype (Po0.05); this was followed by screening of the remaining 1044 samples. Two markers showed significant association with malaria: interleukin-1 alpha þ 4845 G-T (P ¼ 0.035 for mild malaria versus controls) and interleukin-1 beta þ 3953 C-T (P ¼ 0.030 for mild malaria versus severe malaria). Haplotypes constructed using the SNPHAP programme were not associated with any of the malaria phenotypes investigated. In summary, if IL1 variants are involved in malaria susceptibility in the Gambia at all, then the effects are small.

Immunogenetic Control of Antibody Responsiveness in a Malaria Endemic Area

“…It is also possible that a locus in the IL1 gene cluster is involved in control of parasite levels, reflected in alterations of both specific and total antibodies. Polymorphisms in the IL1 gene cluster have been investigated for associations to both severe and mild malaria [8,9], with a polymorphism in IL1B (IL1B ϩ3953 *T) being associated with both parasitemia [8] and severe malaria [9], although no previous associations have been observed with IL1RN [8,9]. There was some evidence for an association between IL10 SNPs and haplotypes and Th2 antibodies.…”

Influence of VEGF‐A gene variation and protein levels in breast cancer susceptibility and severity

“…Kaplan Meier curves, log rank test and Cox proportional hazards models were used for the survival analyses. The haplotype frequencies were estimated using 3 different programs all based on the EM (expectation maximisation) algorithm: SNPHAP, 19,20 Haploview 21 and SimHap 22 were downloaded from http://www. gene.cimr.cam.ac.uk/clayton/software/, http://www.broad.mit.edu/ mpg/haploview/ and http://intranet.waimr.uwa.edu.au/simhap respectively.…”

IL-1 gene cluster polymorphisms and sudden infant death syndrome

“…It is reported that there is a small but significant association between the IL-1␣ ϩ4845 polymorphism and malaria [17,18,20].…”