Association between Chronic Disseminated Candidiasis in Adult Acute Leukemia and Common<i>IL4</i>Promoter Haplotypes

Choi, Eun Hwa; Foster, Charles B.; Taylor, James G.; Erichsen, Hans Christian; Chen, Renee A.; Walsh, Thomas J.; Anttila, Veli Jukka; Ruutu, Tapani; Palotie, Aarno; Chanock, Stephen J.

doi:10.1086/368345

Cited by 51 publications

(48 citation statements)

References 16 publications

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“…For chronic disseminated candidiasis (CDC), a form of invasive infection that occurs primarily in acute leukemia patients undergoing intensive therapy, 4 a genetic contribution to susceptibility has been observed. 5 Additionally, there is some evidence that there is a genetic component affecting susceptibility to systemic candidiasis in humans, as illustrated by the elevated incidence of candidiasis in patients with congenital defects affecting phagocyte function, such as myeloperoxidase deficiency. 6 Mouse models of disseminated candidiasis represent a valuable tool to study the genetic basis of susceptibility to fungal infections.…”

Section: Introductionmentioning

confidence: 99%

Genetic control of suceptibility to Candida albicans in susceptible A/J and resistant C57BL/6J mice

et al. 2005

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The importance of host factors in determining susceptibility to systemic Candida albicans infections is evident in both humans and mice. We have used a mouse model to study the genetic basis of susceptibility, using the inbred strains A/J and C57BL/6J, which are susceptible and resistant, respectively, based on different parameters of the response to infection. To identify genes responsible for this differential host response, brain and kidney fungal load were measured in 128 [A/J Â C57BL/6J] F 2 mice 48 h after infection with 5 Â 10 4 C. albicans blastospores. Segregation analysis in this informative population identified complement component 5 (C5/Hc) as the major gene responsible for this differential susceptibility (LOD of 22.7 for kidney, 19.0 for brain), with a naturally occurring mutation that causes C5 deficiency leading to enhanced susceptibility. C5 was also found to control heart fungal load, survival time, and serum TNF-a levels during infection. Investigation of the response to C. albicans challenge in a series of AcB/BcA recombinant congenic strains validated the importance of C5 in determining the host response. However, the strains BcA67 and BcA72 showed discordant phenotypes with respect to their C5 status, suggesting additional complexity in the genetic control of the inter-strain difference in susceptibility observed in A/J and C57BL/6J following systemic infection with C. albicans. Genes and Immunity (2005) 6, 672-682.

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Section: Introductionmentioning

confidence: 99%

Genetic control of suceptibility to Candida albicans in susceptible A/J and resistant C57BL/6J mice

et al. 2005

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“…8 Common, well-defined candidate genetic variants in innate immune pathways critical for host defense have been identified as risk factors for susceptibility and/or outcome to pathogens, such as malaria, the human immunodeficiency virus, or Candida infection in leukemia patients. [9][10][11] Moreover, common genetic variants in proinflammatory cytokine genes, such as tumor necrosis factor-alpha (TNF), interleukins 6 and 8 (IL6 and IL8) contribute to interindividual differences in circulating levels of these cytokines. 12,13 The reported findings provide correlative data in support of genetic variation as a risk factor for clinical outcome.…”

Section: Introductionmentioning

confidence: 99%

Common genetic variants in the interleukin-6 and chitotriosidase genes are associated with the risk for serious infection in children undergoing therapy for acute myeloid leukemia

et al. 2005

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“…interleukin-4 promoter are associated with chronic disseminated candidiasis, a life-threatening infection in patients with acute leukaemia (Yin et al, 2002;Choi et al, 2003). Association studies have been plagued by an inability to consistently yield reproducible results.…”

Section: Analytical Issues In Snp Studiesmentioning

confidence: 99%

SNPs in cancer research and treatment

2004

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Genetic variation in the human genome is an emerging resource for studying cancer, a complex set of diseases characterised by both environmental and genetic contributions. The number of common germ-line variants is great, on the order of 10 -15 million per person, and represents a remarkable opportunity to investigate the aetiology, interindividual differences in treatment response and outcomes of specific cancers. The study of genetic variation can elucidate critical determinants in environmental exposure and cancer, which could have future implications for preventive and early intervention strategies. However, we are in the initial stages of characterising the tools (i.e., the single-nucleotide polymorphism, SNP) to rigorously analyse the genetic contributions to complex diseases, such as cancer. If the promise of the genomic era is to be realised, we must integrate this information into new strategies for implementation in both public health measures and, most importantly, provision of individual cancer-related care.

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Association between Chronic Disseminated Candidiasis in Adult Acute Leukemia and CommonIL4Promoter Haplotypes

Cited by 51 publications

References 16 publications

Genetic control of suceptibility to Candida albicans in susceptible A/J and resistant C57BL/6J mice

Genetic control of suceptibility to Candida albicans in susceptible A/J and resistant C57BL/6J mice

Common genetic variants in the interleukin-6 and chitotriosidase genes are associated with the risk for serious infection in children undergoing therapy for acute myeloid leukemia

SNPs in cancer research and treatment

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