Nonpathogenic common variants of IFNGR1 and IFNGR2 in association with total serum IgE levels

Harvard University, Cambridge, Massachusetts, United States
Biochemical and Biophysical Research Communications (Impact Factor: 2.3). 10/1999; 263(2):425-9. DOI: 10.1006/bbrc.1999.1368
Source: PubMed


Atopy is an immune disorder in which a Th2 dominant mechanism leads to high IgE levels and the clinical disorder asthma. It has been postulated that the Th1 cytokine IFNgamma, acting through its heterodimeric receptors, IFNgammaR1 and IFNgammaR2, in the induction/proliferation of Th1 cells, might suppress the Th2 responses that may underlie atopic asthma. However, neither murine nor human variants of IFNgamma associate with atopy. Several dysfunctional mutations have been identified in IFNgamma receptor genes (IFNGR1 and IFNGR2) in relation to severe and selective infections with poorly pathogenic organisms. However, little is known about common polymorphisms and their functional role in atopy. To test whether such variants of IFNGR1 and IFNGR2 relate to atopic asthma, we conducted a genetic association study in both British (n = 300) and Japanese (n = 200) populations. An intronic variant of IFNGR1 showed marginal association with total serum IgE levels in the British population compared with those with total IgE levels <30 IU/ml and those with >120-500 IU/ml [odds ratio = 2.00 (95% CI 1. 00-4.07), P = 0.048]. A coding variant, Gln64Arg of the IFNGR2, also associated with total serum IgE levels in the British population [chi(2) = 5.08, P = 0.024]. Further genetic and functional analyses are needed to clarify the role of variants of IFNgamma receptor genes in atopic immune disorder among different ethnic groups.

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Available from: Peisong Gao, Oct 26, 2015
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    • "Rosenzweig et al. demonstrated SNP at position -611 (rs1327474) of IFNGR1 had a stronger effect on the promoter activity than those at position -56 of IFNGR1 [18]. It was also reported that Q64R (rs2070385) of IFNGR2 is a fully functional polymorphism in an in vitro study [19] and associated with total IgE levels [20]. Furthermore, several IL4R polymorphisms, such as Ile50Val (rs1805010), Q576R (rs1801275) and S503P (1805015), have been demonstrated to be associated with a higher risk of atopy and/or atopic asthma [21] [22] [23]. "
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