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Background: Improved understanding of the molecular mechanisms involved in pediatric severe malarial anemia (SMA) pathogenesis is a crucial step in the design of novel therapeutics. Identification of host genetic susceptibility factors in immune regulatory genes offers an important tool for deciphering malaria pathogenesis. The IL-23/IL-17 immune pathway is important for both immunity and erythropoiesis via its effects through IL-23 receptors (IL-23R). However, the impact of IL-23R variants on SMA has not been fully elucidated.

Methods: Since variation within the coding region of IL-23R may influence the pathogenesis of SMA, the association between IL-23R rs1884444 (G/T), rs7530511 (C/T), and SMA (Hb < 6.0 g/dL) was examined in children (n = 369, aged 6-36 months) with P. falciparum malaria in a holoendemic P. falciparum transmission area.

Results: Logistic regression analysis, controlling for confounding factor of anemia, revealed that individual genotypes of IL-23R rs1884444 (G/T) [GT; OR = 1.34, 95% CI = 0.78-2.31, P = 0.304 and TT; OR = 2.02, 95% CI = 0.53-7.74, P = 0.286] and IL-23R rs7530511 (C/T) [CT; OR = 2.6, 95% CI = 0.59-11.86, P = 0.202 and TT; OR = 1.66, 95% CI = 0.84-3.27, P = 0.142] were not associated with susceptibility to SMA. However, carriage of IL-23R rs1884444T/rs7530511T (TT) haplotype, consisting of both mutant alleles, was associated with increased susceptibility to SMA (OR = 1.12, 95% CI = 1.07-4.19, P = 0.030).

Conclusion: Results presented here demonstrate that a haplotype of non-synonymous IL-23R variants increase susceptibility to SMA in children of a holoendemic P. falciparum transmission area.

Titel:	Haplotype of non-synonymous mutations within IL-23R is associated with susceptibility to severe malaria anemia in a P. falciparum holoendemic transmission area of Kenya.
Autor/in / Beteiligte Person:	Munde, EO ; Raballah, E ; Okeyo, WA ; Ong'echa, JM ; Perkins, DJ ; Ouma, C
Link:	Zum Volltext
Zeitschrift:	BMC infectious diseases, Jg. 17 (2017-04-20), Heft 1, S. 291
Veröffentlichung:	London : BioMed Central, [2001-, 2017
Medientyp:	academicJournal
ISSN:	1471-2334 (electronic)
DOI:	10.1186/s12879-017-2404-y
Schlagwort:	Anemia etiology Child, Preschool Female Genetic Predisposition to Disease Genotype Humans Infant Kenya Malaria, Falciparum transmission Male Mutation Anemia genetics Haplotypes Malaria, Falciparum complications Polymorphism, Single Nucleotide Receptors, Interleukin genetics
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [BMC Infect Dis] 2017 Apr 20; Vol. 17 (1), pp. 291. <i>Date of Electronic Publication: </i>2017 Apr 20. MeSH Terms: Haplotypes* ; Polymorphism, Single Nucleotide* ; Anemia / genetics ; Malaria, Falciparum / complications ; Receptors, Interleukin / *genetics ; Anemia / etiology ; Child, Preschool ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Infant ; Kenya ; Malaria, Falciparum / transmission ; Male ; Mutation References: J Clin Microbiol. 2011 Feb;49(2):671-6. (PMID: 21106789) ; Am J Hematol. 2012 Jul;87(7):652-8. (PMID: 22570198) ; Cell Prolif. 2004 Dec;37(6):401-12. (PMID: 15548173) ; Clin Microbiol Rev. 2000 Jul;13(3):439-50. (PMID: 10885986) ; Glob Health Action. 2014 Oct 29;7:25581. (PMID: 25377340) ; Trans R Soc Trop Med Hyg. 2000 Apr;94 Suppl 1:S1-90. (PMID: 11103309) ; Lancet. 2002 Apr 13;359(9314):1311-2. (PMID: 11965279) ; Carcinogenesis. 2012 Dec;33(12):2409-16. (PMID: 23042301) ; Am J Trop Med Hyg. 1993 Sep;49(3):290-300. (PMID: 8372952) ; AIDS. 2006 Jan 9;20(2):275-80. (PMID: 16511422) ; J Clin Endocrinol Metab. 2008 Mar;93(3):1077-81. (PMID: 18073300) ; Am J Trop Med Hyg. 2006 Mar;74(3):376-85. (PMID: 16525094) ; Science. 2006 Dec 1;314(5804):1461-3. (PMID: 17068223) ; Nat Immunol. 2007 Feb;8(2):172-80. (PMID: 17206145) ; Am J Trop Med Hyg. 2007 Dec;77(6 Suppl):23-8. (PMID: 18165471) ; J Immunol. 2008 Apr 15;180(8):5625-35. (PMID: 18390747) ; Curr Opin Hematol. 2009 Nov;16(6):480-7. (PMID: 19812491) ; J Infect Dis. 2006 Jul 15;194(2):198-207. (PMID: 16779726) ; Am J Trop Med Hyg. 2001 Nov;65(5):614-22. (PMID: 11716124) ; Nat Immunol. 2008 Jun;9(6):650-7. (PMID: 18454150) ; Br J Haematol. 1980 Oct;46(2):171-83. (PMID: 7000157) ; Blood. 2002 May 15;99(10):3863-6. (PMID: 11986251) ; PLoS Med. 2006 May;3(5):e158. (PMID: 16605300) ; BMC Infect Dis. 2014 Jun 10;14:316. (PMID: 24912586) ; Immunity. 2004 Oct;21(4):467-76. (PMID: 15485625) ; N Engl J Med. 1995 May 25;332(21):1399-404. (PMID: 7723795) ; Parasitol Int. 2006 Jun;55(2):91-7. (PMID: 16325460) ; Int J Cancer. 2012 Mar 1;130(5):1093-7. (PMID: 21484795) ; Am J Hum Genet. 2007 Feb;80(2):273-90. (PMID: 17236132) ; Trans R Soc Trop Med Hyg. 2005 Apr;99(4):243-51. (PMID: 15708383) ; Q J Med. 1986 Mar;58(227):305-23. (PMID: 3526385) ; Immunology. 2010 Mar;129(3):311-21. (PMID: 20409152) ; N Engl J Med. 2005 Jan 6;352(1):39-47. (PMID: 15635111) ; Curr Hematol Rep. 2004 Mar;3(2):97-106. (PMID: 14965485) ; Genes Immun. 2008 Oct;9(7):631-9. (PMID: 18754016) ; Ann Rheum Dis. 2008 Oct;67(10):1451-4. (PMID: 18199597) ; Growth Factors. 2001;19(1):61-71. (PMID: 11678210) ; J Infect Dis. 1999 Nov;180(5):1753-5. (PMID: 10515852) ; Am J Trop Med Hyg. 1999 Apr;60(4):635-40. (PMID: 10348240) ; J Allergy Clin Immunol. 2007 Aug;120(2):247-54. (PMID: 17666214) ; Trop Med Int Health. 2009 Sep;14(9):1011-9. (PMID: 19552643) ; Physiol Res. 2007;56(3):331-9. (PMID: 16792476) ; J Immunol. 2002 Jun 1;168(11):5699-708. (PMID: 12023369) ; Proc Natl Acad Sci U S A. 2003 May 13;100(10):5986-90. (PMID: 12721360) ; Lancet. 2002 Nov 9;360(9344):1468-75. (PMID: 12433515) ; Br J Haematol. 2006 Apr;133(2):206-9. (PMID: 16611313) ; Mediators Inflamm. 2016;2016:4286576. (PMID: 27418744) ; Am J Trop Med Hyg. 1994 May;50(5):529-36. (PMID: 7911282) ; Immunity. 2000 Nov;13(5):715-25. (PMID: 11114383) ; Nat Rev Genet. 2002 Aug;3(8):611-21. (PMID: 12154384) ; Clin Immunol. 2008 Feb;126(2):211-21. (PMID: 17945537) ; Semin Immunol. 2007 Dec;19(6):400-8. (PMID: 18166487) ; Eur Cytokine Netw. 2004 Jul-Sep;15(3):247-54. (PMID: 15542450) ; Mol Carcinog. 2010 Oct;49(10):862-8. (PMID: 20607725) ; Immunol Res. 2012 Apr;52(1-2):34-41. (PMID: 22392050) ; J Immunol. 2006 May 1;176(9):5652-61. (PMID: 16622035) ; Am J Trop Med Hyg. 1999 Dec;61(6):932-40. (PMID: 10674673) ; Hum Genet. 2007 Sep;122(2):201-6. (PMID: 17587057) ; Zhonghua Yi Xue Za Zhi. 2015 May 26;95(20):1576-80. (PMID: 26463605) ; Blut. 1983 May;46(5):279-88. (PMID: 6340761) ; Infect Immun. 2012 Dec;80(12):4435-43. (PMID: 23045477) ; Am J Trop Med Hyg. 1999 May;60(5):733-7. (PMID: 10344643) ; Genes Immun. 2005 Sep;6(6):462-6. (PMID: 15933743) Grant Information: D43 TW005884 United States TW FIC NIH HHS; R01 TW008306 United States TW FIC NIH HHS Contributed Indexing: Keywords: Exon; Genotypes; Haplotypes; Il-23R Substance Nomenclature: 0 (IL23R protein, human) ; 0 (Receptors, Interleukin) Entry Date(s): Date Created: 20170422 Date Completed: 20170807 Latest Revision: 20181202 Update Code: 20240513 PubMed Central ID: PMC5397818

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Haplotype of non-synonymous mutations within IL-23R is associated with susceptibility to severe malaria anemia in a P. falciparum holoendemic transmission area of Kenya.