Polymorphism in intron 1 of the interferon-gamma gene influences both serum immunoglobulin E levels and the risk for chronic hepatitis B virus infection in Polynesians
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Intron 1 of the interferon-gamma (IFNG) gene contains two polymorphisms. The 12 CA-repeat allele of the +875 IFNGCA microsatellite and the T allele of the +A874T single nucleotide polymorphism (SNP) have been associated with increased in vitro IFNG production and a variety of clinical phenotypes. The purpose of this study was to determine whether these polymorphisms influence total serum IgE levels [tsIgE] and the outcome of a hepatitis B virus (HBV) infection. IFNGCA and +A874T were typed in 186 asthmatics of Niuean ancestry and in Polynesian women with a chronic HBV infection (n = 60) and with natural immunity to the HBV (n = 66). The IFNGCA genotype was associated with [tsIgE] in asthmatic children (n = 51, p = 0.004) but not adults (n = 135, p = 0.87). The data were consistent with a co-dominant influence of the 12 CA-repeat allele on high [tsIgE]. The IFNGCA genotype was also associated with the risk for chronic HBV infection (χ 2 = 11.6, p = 0.003) because of a dominant effect of the 12 CA-repeat allele on developing natural immunity in homozygotes (OR = 5.8, p = 0.003) and heterozygotes (OR = 2.7, p = 0.01). Similar associations were found for the T allele of the +A874T SNP. The possibility that these associations were due to linked alleles in the adjacent 783 bp of the promoter and 3′-untranslated region of the IFNG gene was excluded by direct sequencing. In summary, high-IFNG-producing alleles in intron 1 of the IFNG locus are associated with high [tsIgE] in asthmatic children from Niue and with natural immunity to the HBV in Polynesian women. These findings are consistent with a previous report of an association between +875 IFNGCA and [tsIgE] and provide preliminary evidence of a new association with the outcome of an HBV infection.
KeywordsInterferon gamma Immunoglobulin E Hepatitis B virus Niue Polynesia
We would like to thank Malama Nilau for recruiting study subjects from the Niuean community. We would like to thank Liam Williams and Kristine Boxen for technical assistance. We are particularly grateful to the volunteers.
Dr. Abbott was awarded the Harold Thomas Rotary Research Fellowship by the National Child Health Research Foundation to begin this work, which was also supported by the Lloyd Morgan Lions Clubs Charitable Trust New Zealand, the Maurice and Phyllis Paykel Trust, the Auckland Medical Research Foundation and the Auckland Asthma Society. We also wish to acknowledge helpful discussions with Dr. David Duffy and Professor W.O.M. Cookson. All experiments were performed in accordance with the laws of New Zealand.
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