A functional promoter variant in IL12B predisposes to cerebral malaria

Human Molecular Genetics
Sandrine MarquetAlain J Dessein

Abstract

The role of the Th1 pathway in the pathogenesis of severe malaria is unclear. We recently reported that a polymorphism with increasing IFNG transcription is associated with protection against cerebral malaria (CM). Interleukin-12 is required for Th1 cell differentiation, which is characterized by the production of interferon-gamma. We investigated 21 markers in IL12-related genes, including IL12A and IL12B encoding the two IL-12 (IL12p70) subunits, IL12p35 and IL12p40. We performed a family-based association study using a total sample set of 240 nuclear families. The IL12Bpro polymorphism was associated with susceptibility to CM. The CTCTAA allele and the GC/CTCTAA genotype are over-transmitted to children with CM (P = 0.0002 and 0.00002, respectively). We estimated the odds ratio to be 2.11 for risk of CM in heterozygous children [(95% confidence interval, 1.49-2.99); P < 0.0001]. Although the CTCTAA allele had a dominant effect on CM susceptibility, this effect is much stronger in heterozygous children, consistent with the functional effects of this allele in a heterozygous form. Heterozygosity for this polymorphism has been associated with reduced expression of the gene encoding IL12p40 and a low level of IL12p70 production....Continue Reading

References

Jan 1, 1997·Infection and Immunity·P PerlmannM Troye-Blomberg
Jun 25, 1999·Molecular Genetics and Metabolism·D E ComingsW R Peters
Jun 17, 2000·Infection and Immunity·A J LutyP G Kremsner
Sep 26, 2000·Molecular Genetics and Metabolism·D E Comings, J P MacMurray
Apr 21, 2001·European Journal of Human Genetics : EJHG·S HorvathN M Laird
Jun 5, 2001·The American Journal of Tropical Medicine and Hygiene·Y MaenoM Aikawa
Feb 8, 2002·Nature·Louis H MillerOgobara K Doumbo
Feb 4, 2003·Nature Reviews. Immunology·Giorgio Trinchieri
Feb 22, 2003·Human Genetics·Mitsuteru AkahoshiMine Harada
Oct 21, 2003·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Linda HibbertRobert A Kastelein
Dec 6, 2003·Proceedings of the National Academy of Sciences of the United States of America·Sophie LucasFrédéric J de Sauvage
Jan 28, 2004·Nature Medicine·Terrie E TaylorJeffrey G Mueller
Apr 23, 2004·The Journal of Investigative Dermatology·Nicolle H R LitjensPeter H Nibbering
Jun 4, 2004·Genes and Immunity·J Müller-BerghausD Schadendorf
Aug 7, 2004·Bioinformatics·J C BarrettM J Daly
Aug 24, 2004·American Journal of Human Genetics·Adrienne G RandolphScott T Weiss
Aug 10, 2005·The Journal of Infectious Diseases·Sandrine CabantousSandrine Marquet
Oct 8, 2005·The Journal of Allergy and Clinical Immunology·Tomomitsu HirotaMayumi Tamari
Mar 8, 2006·Immunology and Cell Biology·Judy C PengRanjeny Thomas

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Citations

Aug 30, 2008·The Journal of Infectious Diseases·Sunil Parikh, Philip J Rosenthal
May 5, 2012·Malaria Journal·Gregory MacMullinDylan R Pillai
Dec 4, 2009·Genes and Immunity·G MorahanUNKNOWN Type I Diabetes Genetics Consortium
Jan 15, 2013·Journal of Tropical Medicine·Vitor R R de MendonçaManoel Barral-Netto
Jun 26, 2009·Cellular & Molecular Biology Letters·Zlatka Georgieva DobrevaLyuba Dineva Miteva
Aug 15, 2015·Malaria Journal·Vitor R R MendonçaManoel Barral-Netto
Aug 28, 2013·Medical Hypotheses·Yuri Chaves Martins, Cláudio Tadeu Daniel-Ribeiro
Jan 29, 2014·Fluids and Barriers of the CNS·Manuela Polimeni, Mauro Prato
Apr 10, 2016·Scandinavian Journal of Immunology·A Paradowska-GoryckaP P Jagodzinski
Feb 22, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Quanju ZhaoXiaojing Ma
Dec 17, 2015·Infection and Immunity·Sandrine MarquetAlain J Dessein
Sep 1, 2008·Expert Review of Clinical Immunology·Steven J Schrodi
Jul 20, 2018·Scientific Reports·Yong SongGuicheng Brad Zhang
Jan 13, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mathilde FauconnierValérie F J Quesniaux

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