A mutation in the leptin receptor is associated with Entamoeba histolytica infection in children

Priya Duggal, Xiaoti Guo, Rashidul Haque, Kristine M. Peterson, Stacy Ricklefs, Dinesh Mondal, Faisal Alam, Zannatun Noor, Hans P. Verkerke, Chelsea Marie, Charles A. Leduc, Streamson C. Chua, Jr., Martin G. Myers, Rudolph L. Leibel, Eric Houpt, Carol A. Gilchrist, Alan Sher, Stephen F. Porcella, William A. Petri

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Abstract

Malnutrition substantially increases susceptibility to Entamoeba histolytica in children. Leptin is a hormone produced by adipocytes that inhibits food intake, influences the immune system, and is suppressed in malnourished children. Therefore we hypothesized that diminished leptin function may increase susceptibility to E. histolytica infection. We prospectively observed a cohort of children, beginning at preschool age, for infection by the parasite E. histolytica every other day over 9 years and evaluated them for genetic variants in leptin (LEP) and the leptin receptor (LEPR). We found increased susceptibility to intestinal infection by this parasite associated with an amino acid substitution in the cytokine receptor homology domain 1 of LEPR. Children carrying the allele for arginine (223R) were nearly 4 times more likely to have an infection compared with those homozygous for the ancestral glutamine allele (223Q). An association of this allele with amebic liver abscess was also determined in an independent cohort of adult patients. In addition, mice carrying at least 1 copy of the R allele of Lepr were more susceptible to infection and exhibited greater levels of mucosal destruction and intestinal epithelial apoptosis after amebic infection. These findings suggest that leptin signaling is important in mucosal defense against amebiasis and that polymorphisms in the leptin receptor explain differences in susceptibility of children in the Bangladesh cohort to amebiasis.

Original languageEnglish (US)
Pages (from-to)1191-1198
Number of pages8
JournalJournal of Clinical Investigation
Volume121
Issue number3
DOIs
StatePublished - Mar 1 2011

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Leptin Receptors
Entamoeba histolytica
Leptin
Mutation
Alleles
Infection
Amebiasis
Parasitic Diseases
Amoebic Liver Abscess
Cytokine Receptors
Bangladesh
Amino Acid Substitution
Glutamine
Adipocytes
Malnutrition
Arginine
Immune System
Eating
Hormones
Apoptosis

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Duggal, P., Guo, X., Haque, R., Peterson, K. M., Ricklefs, S., Mondal, D., ... Petri, W. A. (2011). A mutation in the leptin receptor is associated with Entamoeba histolytica infection in children. Journal of Clinical Investigation, 121(3), 1191-1198. https://doi.org/10.1172/JCI45294

A mutation in the leptin receptor is associated with Entamoeba histolytica infection in children. / Duggal, Priya; Guo, Xiaoti; Haque, Rashidul; Peterson, Kristine M.; Ricklefs, Stacy; Mondal, Dinesh; Alam, Faisal; Noor, Zannatun; Verkerke, Hans P.; Marie, Chelsea; Leduc, Charles A.; Chua, Jr., Streamson C.; Myers, Martin G.; Leibel, Rudolph L.; Houpt, Eric; Gilchrist, Carol A.; Sher, Alan; Porcella, Stephen F.; Petri, William A.

In: Journal of Clinical Investigation, Vol. 121, No. 3, 01.03.2011, p. 1191-1198.

Research output: Contribution to journalArticle

Duggal, P, Guo, X, Haque, R, Peterson, KM, Ricklefs, S, Mondal, D, Alam, F, Noor, Z, Verkerke, HP, Marie, C, Leduc, CA, Chua, Jr., SC, Myers, MG, Leibel, RL, Houpt, E, Gilchrist, CA, Sher, A, Porcella, SF & Petri, WA 2011, 'A mutation in the leptin receptor is associated with Entamoeba histolytica infection in children', Journal of Clinical Investigation, vol. 121, no. 3, pp. 1191-1198. https://doi.org/10.1172/JCI45294
Duggal, Priya ; Guo, Xiaoti ; Haque, Rashidul ; Peterson, Kristine M. ; Ricklefs, Stacy ; Mondal, Dinesh ; Alam, Faisal ; Noor, Zannatun ; Verkerke, Hans P. ; Marie, Chelsea ; Leduc, Charles A. ; Chua, Jr., Streamson C. ; Myers, Martin G. ; Leibel, Rudolph L. ; Houpt, Eric ; Gilchrist, Carol A. ; Sher, Alan ; Porcella, Stephen F. ; Petri, William A. / A mutation in the leptin receptor is associated with Entamoeba histolytica infection in children. In: Journal of Clinical Investigation. 2011 ; Vol. 121, No. 3. pp. 1191-1198.
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AU - Alam, Faisal

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AU - Leduc, Charles A.

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AU - Myers, Martin G.

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