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

Lehrnbecher, Thomas; Bernig, Toralf; Hanisch, Mitra; Koehl, Ulrike; Behl, Michael; Reinhardt, Dirk; Creutzig, Ursula; Klingebiel, Thomas; Chanock, Stephen J.; Schwabe, Dirk

doi:10.1038/sj.leu.2403922

Cited by 55 publications

(48 citation statements)

References 34 publications

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“…This supports the existence of a 'healthy aging' phenotype in which individuals somehow delay or avoid major clinical disease and disability until late in life. Although previous studies have suggested that CHIT-1-deficient individuals show a certain degree of disadvantage, such as increased susceptibility to parasitic disease infections, to microorganisms containing chitin and to Gram-negative infections, 17,[31][32][33][34][35] other studies indicate that CHIT-1 deficiency is not a disadvantage but rather a selective advantage. [36][37] Given the very high gene frequency of the main mutant allele, as shown in this study, it seems more likely that in humans, selection has occurred in the direction of decreasing or eliminating the activity of this enzyme.…”

Section: Discussionmentioning

confidence: 93%

Human chitotriosidase polymorphism is associated with human longevity in Mediterranean nonagenarians and centenarians

et al. 2009

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Human phagocyte-specific chitotriosidase (CHIT-1) is a chitinolytic enzyme associated with several diseases involving macrophage activation. Previous studies have demonstrated that a high activity of Chit could have widespread effects on atherosclerosis, cardiovascular disease and dementia. The 24-bp duplication in the CHIT-1 gene is associated with a deficiency in enzymatic activity. In this study, we attempted to assess whether CHIT-1 could be a plausible candidate gene responsible for human longevity. Therefore, we compared the distribution of the CHIT-1 polymorphism genotype in three different populations of the Mediterranean area (Italian, Greek and Tunisian) aged over 90 years. As a control group for each nonagenarian and centenarian, a 60-70-year-old subject was genotyped. We found that the heterozygote frequency for the 24-bp duplication in the CHIT-1 gene was not significantly different among the oldest old subjects of Mediterranean populations, whereas it was significantly different between oldest old subjects and control subjects, being highest among the oldest old subjects and lowest among control groups. In the oldest old group, no subject was observed to be homozygous for CHIT-1 deficiency. Moreover, the mean enzymatic activity in heterozygous oldest subjects was lower than that in the control group. These data indicate that the heterozygosis for a 24-bp duplication in the CHIT-1 gene could have a protective effect in human longevity.

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Section: Discussionmentioning

confidence: 93%

Human chitotriosidase polymorphism is associated with human longevity in Mediterranean nonagenarians and centenarians

et al. 2009

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“…Overall, these findings suggest a possible use of recombinant chitotriosidase to treat life-threatening fungal infections [56]. Finally, adding to the list of findings demonstrating a role of ChT in the immune response, functionally important variants in ChT alleles have been shown to influence the susceptibility to infections with Gram-negative bacteria [57]. Other members of chitinase family are also likely to be involved in the immune response, e.g.…”

Section: Cht and Immunitymentioning

confidence: 96%

Chitotriosidase: the yin and yang

Malaguarnera

2006

Cell. Mol. Life Sci.

111

100

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The enzyme chitotriosidase (ChT), the human analogue of chitinases from non-vertebrate species, is one of the most abundant and indicative proteins secreted by activated macrophages. Its enzymatic activity is elevated in serum of patients suffering from Gaucher's disease type 1 and in some other inherited lysosomal storage disorders, as well as in diseases in which macrophages are activated. The last decade has witnessed the appearance of a substantial number of studies attempting to unravel its cellular functions, which have yet not been fully defined. A great deal of progress has been made in the study of the physiological roles of ChT. This review is looks at the key areas of investigations addressed to further illuminate whether ChT activation might have different functional meanings in various diseases.

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“…These cytokines can modulate lymphoid development and immune function. [3][4][5][6][7][8][9][10] Since immune dysfunction is thought to be at the underlying basis of lymphomagenesis, an imbalance in the regulation and expression of Th1 and Th2 cytokines, which are the fundamental messengers of adaptive immunity, could play an important role in the etiology of non-Hodgkin lymphoma (NHL) and its major subtypes. 11,12 Genetic variation is common across the human genome.…”

Section: Introductionmentioning

confidence: 99%

“…13 These functional variants may alter disease risk, affect the observed phenotype, contribute to the pathogenesis of the disease, or alter the response to treatment. 3,6,10,[14][15][16][17][18][19] Common genetic variants in candidate genes, or for that matter, pathways of genes, can be applied to genetic association studies in search of genetic risk factors for disease susceptibility. Since the expression of Th1 and Th2 cytokines can be altered by germ-line genetic variants, 5 we studied the association between common polymorphisms in Th1 and Th2 cytokine genes and the risk of NHL.…”

Section: Introductionmentioning

confidence: 99%

Cytokine polymorphisms in the Th1/Th2 pathway and susceptibility to non-Hodgkin lymphoma

Lan

Zheng

Rothman

et al. 2006

Blood

168

140

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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

Cited by 55 publications

References 34 publications

Human chitotriosidase polymorphism is associated with human longevity in Mediterranean nonagenarians and centenarians

Human chitotriosidase polymorphism is associated with human longevity in Mediterranean nonagenarians and centenarians

Chitotriosidase: the yin and yang

Cytokine polymorphisms in the Th1/Th2 pathway and susceptibility to non-Hodgkin lymphoma

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