Siew-Kim Khoo1, Mika Mäkelä2, David Chandler3, En Nee Schultz4, Sarra E Jamieson5, Jack Goldblatt6, Tari Haahtela2, Peter LeSouëf4, Guicheng Zhang7,8,9,10. 1. School of Paediatrics and Child Health, The University of Western Australia, Perth, WA, Australia. Kim.Khoo@telethonkids.org.au. 2. Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, Finland. 3. Australian Genome Research Facility Ltd, Perth, WA, Australia. 4. School of Paediatrics and Child Health, The University of Western Australia, Perth, WA, Australia. 5. Telethon Kids Institute, Centre for Child Health Research, The University of Western Australia, Perth, WA, Australia. 6. Genetic Services & Familial Cancer Program of Western Australia, King Edward Memorial Hospital for Women, Perth, WA, Australia. 7. School of Paediatrics and Child Health, The University of Western Australia, Perth, WA, Australia. brad.zhang@curtin.edu.au. 8. Telethon Kids Institute, Centre for Child Health Research, The University of Western Australia, Perth, WA, Australia. brad.zhang@curtin.edu.au. 9. School of Public Health, Curtin University, Perth, WA, Australia. brad.zhang@curtin.edu.au. 10. Centre for Genetic Origins of Health and Disease, Curtin University and the University of Western Australia, Perth, WA, Australia. brad.zhang@curtin.edu.au.
Abstract
BACKGROUND: Finnish and Russian Karelian children have a highly contrasting occurrence of asthma and allergy. In these two environments, we studied associations between total serum immunoglobulin E (IgE) with methylation levels in cluster of differentiation 14 (CD14). METHODS: Five hundred Finnish and Russian Karelian children were included in four groups: Finnish children with high IgE (n = 126) and low IgE (n = 124) as well as Russian children with high IgE (n = 125) and low IgE (n = 125). DNA was extracted from whole blood cells and pyrosequenced. Three CpG sites were selected in the promoter region of CD14. RESULTS: Methylation levels in two of the three CpG sites were higher in the Finnish compared to Russian Karelian children. In the promoter area of CD14, the Finnish compared to Russian children with low IgE had a significant (p < 0.0001) increase in methylation levels at the Amp5Site 2. Likewise, the Finnish compared to Russian children with high IgE had a significant (p = 0.003) increase in methylation levels at the Amp5Site 3. In Russian children with low vs. high IgE, there were significant differences in methylation levels, but this was not the case on the Finnish side. In the regression analysis, adding the methylation variation of CD14 to the model did not explain the higher asthma and allergy risk in the Finnish children. CONCLUSIONS: The methylation levels in the promoter region of CD14 gene were higher in the Finnish compared to Russian Karelian children. However, the methylation variation of this candidate gene did not explain the asthma and allergy contrast between these two areas.
BACKGROUND: Finnish and Russian Karelian children have a highly contrasting occurrence of asthma and allergy. In these two environments, we studied associations between total serum immunoglobulin E (IgE) with methylation levels in cluster of differentiation 14 (CD14). METHODS: Five hundred Finnish and Russian Karelian children were included in four groups: Finnish children with high IgE (n = 126) and low IgE (n = 124) as well as Russian children with high IgE (n = 125) and low IgE (n = 125). DNA was extracted from whole blood cells and pyrosequenced. Three CpG sites were selected in the promoter region of CD14. RESULTS: Methylation levels in two of the three CpG sites were higher in the Finnish compared to Russian Karelian children. In the promoter area of CD14, the Finnish compared to Russian children with low IgE had a significant (p < 0.0001) increase in methylation levels at the Amp5Site 2. Likewise, the Finnish compared to Russian children with high IgE had a significant (p = 0.003) increase in methylation levels at the Amp5Site 3. In Russian children with low vs. high IgE, there were significant differences in methylation levels, but this was not the case on the Finnish side. In the regression analysis, adding the methylation variation of CD14 to the model did not explain the higher asthma and allergy risk in the Finnish children. CONCLUSIONS: The methylation levels in the promoter region of CD14 gene were higher in the Finnish compared to Russian Karelian children. However, the methylation variation of this candidate gene did not explain the asthma and allergy contrast between these two areas.
Authors: Hani Harb; Bilal Alashkar Alhamwe; Daniel P Potaczek; Annika Scheynius; Nathalie Acevedo; Paolo Frumento; Catharina Johansson; Lisa Eick; Nikos Papadogiannakis; Johan Alm; Harald Renz Journal: Biomed Res Int Date: 2019-04-17 Impact factor: 3.411
Authors: Jean Bousquet; Clive Grattan; Thomas Bieber; Paolo Matricardi; Hans Uwe Simon; Ulrich Wahn; Antonella Muraro; Peter W Hellings; Ioana Agache Journal: Clin Transl Allergy Date: 2017-12-02 Impact factor: 5.871