IFNGR1 polymorphisms in Thai malaria patients
INFECTION GENETICS AND EVOLUTION
Authors: Naka, Izumi; Patarapotikul, Jintana; Hananantachai, Hathairad; Tokunaga, Katsushi; Tsuchiya, Naoyuki; Ohashi, Jun
Abstract
Interferon-gamma (IFN-gamma) has been suggested to play an important role in the pathogenesis of malaria. To examine possible association of the IFN-gamma receptor 1 (IFNGR1) polymorphisms with cerebral malaria, 312 adult patients with Plasm odium falciparum malaria (203 mild and 109 cerebral malaria patients) living in northwest Thailand were genotyped for six single nucleotide polymorphisms (SNPs) including -56T/C (rs2234711) and a microsatellite marker in IFNGR1. A case-control association analysis failed to detect significant association between the IFNGR1 polymorphisms and cerebral malaria, thus implying that the IFNGR1 polymorphism may not be a major genetic factor influencing the development of cerebral malaria in the Thai population. These data also provide useful information for future genetic studies of IFNG polymorphisms in Thai patients. (C) 2009 Elsevier B.V. All rights reserved.
No significant impact of IFN-gamma pathway gene variants on tuberculosis susceptibility in a West African population
EUROPEAN JOURNAL OF HUMAN GENETICS
Authors: Meyer, Christian G.; Intemann, Christopher D.; Foerster, Birgit; Owusu-Dabo, Ellis; Franke, Andre; Horstmann, Rolf D.; Thye, Thorsten
Abstract
The concept of interferon-gamma (IFN-gamma) having a central role in cell-mediated immune defence to Mycobacterium tuberculosis has long been proposed. Observations made through early candidate gene studies of constituents of the IFN-gamma pathway have identified moderately associated variants associated with resistance or susceptibility to tuberculosis (TB). By analysing 20 major genes whose proteins contribute to IFN-gamma signalling we have assessed a large fraction of the variability in genes that might contribute to susceptibility to TB. Genetic variants were identified by sequencing the promoter regions and all exons of IFNG, IFNGR1, IFNGR2, IRF1, IL12A, IL12B, IL12RB1, IL12RB2, IL23A, IL23R, IL27, EBI3, IL27RA, IL6ST, SOCS1, STAT1, STAT4, JAK2, TYK2 and TBX21 in 69 DNA samples from Ghana. In addition, we screened all exons of IFNGR1 in a Ghanaian study group comprising 1999 TB cases and 2589 controls by high-resolution melting point analysis. The fine-mapping approach allows for a detailed screening of all variants, common and rare. Statistical comparisons of cases and controls, however, did not yield significant results after correction for multiple testing with any of the 246 variants selected for genotyping in this investigation. Gene-wise haplotype tests and analysis of rare variants did not reveal any significant association with susceptibility to TB in our investigation as well. Although this analysis was applied on a plausible set of IFN-gamma pathway genes in the largest African TB cohort available so far, the lack of significant results challenges the view that genetic marker of the IFN-gamma pathway have an important impact on susceptibility to TB.