No simple answers for the Finnish and Russian Karelia allergy contrast: Methylation of CD14 gene
Corresponding Author
Siew-Kim Khoo
School of Paediatrics and Child Health, The University of Western Australia, Perth, WA, Australia
Correspondence
Guicheng Zhang, School of Public Health, Curtin University, Kent St Bentley, WA 6102, Australia
Tel.: 61-892663226
Fax: 61-893882097
E-mail: [email protected]
and
Siew-Kim Khoo, School of Paediatrics and Child Health, The University of Western Australia, GPO Box D184, Perth, WA 6840, Australia
Tel.: 61-894897875
Fax: 61-893882097
E-mail: [email protected]
Search for more papers by this authorMika Mäkelä
Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, Finland
Search for more papers by this authorDavid Chandler
Australian Genome Research Facility Ltd, Perth, WA, Australia
Search for more papers by this authorEn Nee Schultz
School of Paediatrics and Child Health, The University of Western Australia, Perth, WA, Australia
Search for more papers by this authorSarra E. Jamieson
Telethon Kids Institute, Centre for Child Health Research, The University of Western Australia, Perth, WA, Australia
Search for more papers by this authorJack Goldblatt
Genetic Services & Familial Cancer Program of Western Australia, King Edward Memorial Hospital for Women, Perth, WA, Australia
Search for more papers by this authorTari Haahtela
Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, Finland
Search for more papers by this authorPeter LeSouëf
School of Paediatrics and Child Health, The University of Western Australia, Perth, WA, Australia
Search for more papers by this authorCorresponding Author
Guicheng Zhang
School of Paediatrics and Child Health, The University of Western Australia, Perth, WA, Australia
Telethon Kids Institute, Centre for Child Health Research, The University of Western Australia, Perth, WA, Australia
School of Public Health, Curtin University, Perth, WA, Australia
Centre for Genetic Origins of Health and Disease, Curtin University and the University of Western Australia, Perth, WA, Australia
Correspondence
Guicheng Zhang, School of Public Health, Curtin University, Kent St Bentley, WA 6102, Australia
Tel.: 61-892663226
Fax: 61-893882097
E-mail: [email protected]
and
Siew-Kim Khoo, School of Paediatrics and Child Health, The University of Western Australia, GPO Box D184, Perth, WA 6840, Australia
Tel.: 61-894897875
Fax: 61-893882097
E-mail: [email protected]
Search for more papers by this authorCorresponding Author
Siew-Kim Khoo
School of Paediatrics and Child Health, The University of Western Australia, Perth, WA, Australia
Correspondence
Guicheng Zhang, School of Public Health, Curtin University, Kent St Bentley, WA 6102, Australia
Tel.: 61-892663226
Fax: 61-893882097
E-mail: [email protected]
and
Siew-Kim Khoo, School of Paediatrics and Child Health, The University of Western Australia, GPO Box D184, Perth, WA 6840, Australia
Tel.: 61-894897875
Fax: 61-893882097
E-mail: [email protected]
Search for more papers by this authorMika Mäkelä
Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, Finland
Search for more papers by this authorDavid Chandler
Australian Genome Research Facility Ltd, Perth, WA, Australia
Search for more papers by this authorEn Nee Schultz
School of Paediatrics and Child Health, The University of Western Australia, Perth, WA, Australia
Search for more papers by this authorSarra E. Jamieson
Telethon Kids Institute, Centre for Child Health Research, The University of Western Australia, Perth, WA, Australia
Search for more papers by this authorJack Goldblatt
Genetic Services & Familial Cancer Program of Western Australia, King Edward Memorial Hospital for Women, Perth, WA, Australia
Search for more papers by this authorTari Haahtela
Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, Finland
Search for more papers by this authorPeter LeSouëf
School of Paediatrics and Child Health, The University of Western Australia, Perth, WA, Australia
Search for more papers by this authorCorresponding Author
Guicheng Zhang
School of Paediatrics and Child Health, The University of Western Australia, Perth, WA, Australia
Telethon Kids Institute, Centre for Child Health Research, The University of Western Australia, Perth, WA, Australia
School of Public Health, Curtin University, Perth, WA, Australia
Centre for Genetic Origins of Health and Disease, Curtin University and the University of Western Australia, Perth, WA, Australia
Correspondence
Guicheng Zhang, School of Public Health, Curtin University, Kent St Bentley, WA 6102, Australia
Tel.: 61-892663226
Fax: 61-893882097
E-mail: [email protected]
and
Siew-Kim Khoo, School of Paediatrics and Child Health, The University of Western Australia, GPO Box D184, Perth, WA 6840, Australia
Tel.: 61-894897875
Fax: 61-893882097
E-mail: [email protected]
Search for more papers by this authorAbstract
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.
Supporting Information
Filename | Description |
---|---|
pai12612-sup-0001-TableS1-S5.docxWord document, 21 KB |
Table S1. PCR and sequencing primer sequences for pyrosequencing assays Table S2. Primer sequences for pyrosequencing assays. Table S3. Odds ratios of Finnish vs. Russian (Fin/Rus) environment for asthmatic/allergic conditions in Karelian children. Table S4. The comparison of the results in the whole population and the half of the population in Russian and Finnish children*. Table S5. The comparison of the results in the whole population and the half of the population in children with low and high total serum IgE*. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1Asher MI, Montefort S, Bjorksten B, et al. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC phases one and three repeat multicountry cross-sectional surveys. Lancet (London, England) 2006: 368: 733–43.
- 2Ernst P, Cormier Y. Relative scarcity of asthma and atopy among rural adolescents raised on a farm. Am J Respir Crit Care Med 2000: 161: 1563–6.
- 3Von Ehrenstein OS, Von Mutius E, Illi S, Baumann L, Bohm O, von Kries R. Reduced risk of hay fever and asthma among children of farmers. Clin Exp Allergy 2000: 30: 187–93.
- 4Yemaneberhan H, Bekele Z, Venn A, Lewis S, Parry E, Britton J. Prevalence of wheeze and asthma and relation to atopy in urban and rural Ethiopia. Lancet (London, England) 1997: 350: 85–90.
- 5Zhang G, Candelaria P, Makela JM, et al. Disparity of innate immunity-related gene effects on asthma and allergy on Karelia. Pediatr Allergy Immunol 2011: 22: 621–30.
- 6Zhang G, Khoo SK, Makela MJ, et al. Maternal genetic variants of IL4/IL13 pathway genes on IgE with “western or eastern environments/lifestyles”. Allergy Asthma Immunol Res 2014: 6: 350–6.
- 7Strachan DP. Family size, infection and atopy: the first decade of the “hygiene hypothesis”. Thorax 2000: 55(Suppl 1): S2–10.
- 8Martinez FD. CD14, endotoxin, and asthma risk: actions and interactions. Proc Am Thorac Soc 2007: 4: 221–5.
- 9Vercelli D. Advances in asthma and allergy genetics in 2007. J Allergy Clin Immunol 2008: 122: 267–71.
- 10Vercelli D. Discovering susceptibility genes for asthma and allergy. Nat Rev Immunol 2008: 8: 169–82.
- 11Martin AC, Laing IA, Khoo SK, et al. Acute asthma in children: relationships among CD14 and CC16 genotypes, plasma levels, and severity. Am J Respir Crit Care Med 2006: 173: 617–22.
10.1164/rccm.200509-1367OC Google Scholar
- 12Zhang G, Khoo SK, Laatikainen T, et al. Opposite gene by environment interactions in Karelia for CD14 and CC16 single nucleotide polymorphisms and allergy. Allergy 2009: 64: 1333–41.
- 13Lau MY, Dharmage SC, Burgess JA, et al. CD14 polymorphisms, microbial exposure and allergic diseases: a systematic review of gene-environment interactions. Allergy 2014: 69: 1440–53.
- 14Smit LA, Siroux V, Bouzigon E, et al. CD14 and toll-like receptor gene polymorphisms, country living, and asthma in adults. Am J Respir Crit Care Med 2009: 179: 363–8.
10.1164/rccm.200810-1533OC Google Scholar
- 15Zhang G, Goldblatt J, LeSouef PN. Does the relationship between IgE and the CD14 gene depend on ethnicity? Allergy 2008: 63: 1411–7.
- 16Haahtela T, Laatikainen T, Alenius H, et al. Hunt for the origin of allergy - comparing the Finnish and Russian Karelia. Clin Exp Allergy 2015: 45: 891–901.
- 17Pekkarinen PT, von Hertzen L, Laatikainen T, et al. A disparity in the association of asthma, rhinitis, and eczema with allergen-specific IgE between Finnish and Russian Karelia. Allergy 2007: 62: 281–7.
- 18von Hertzen L, Laatikainen T, Pitkanen T, et al. Microbial content of drinking water in Finnish and Russian Karelia - implications for atopy prevalence. Allergy 2007: 62: 288–92.
- 19von Hertzen L, Makela MJ, Petays T, et al. Growing disparities in atopy between the Finns and the Russians: a comparison of 2 generations. J Allergy Clin Immunol 2006: 117: 151–7.
- 20Baldini M, Lohman IC, Halonen M, Erickson RP, Holt PG, Martinez FD. A Polymorphism* in the 5′ flanking region of the CD14 gene is associated with circulating soluble CD14 levels and with total serum immunoglobulin E. Am J Respir Cell Mol Biol 1999: 20: 976–83.
- 21Guerra S, Carla Lohman I, LeVan TD, Wright AL, Martinez FD, Halonen M. The differential effect of genetic variation on soluble CD14 levels in human plasma and milk. Am J Reprod Immunol 2004: 52: 204–11.
- 22Munthe-Kaas MC, Bertelsen RJ, Torjussen TM, et al. Pet keeping and tobacco exposure influence CD14 methylation in childhood. Pediatr Allergy Immunol 2012: 23: 747–54.
- 23Seiskari T, Kondrashova A, Viskari H, et al. Allergic sensitization and microbial load–a comparison between Finland and Russian Karelia. Clin Exp Immunol 2007: 148: 47–52.
- 24Pakarinen J, Hyvarinen A, Salkinoja-Salonen M, et al. Predominance of gram-positive bacteria in house dust in the low-allergy risk Russian Karelia. Environ Microbiol 2008: 10: 3317–25.
- 25Simpson A, Martinez FD. The role of lipopolysaccharide in the development of atopy in humans. Clin Exp Allergy 2010: 40: 209–23.
- 26Hugg T, Ruotsalainen R, Jaakkola MS, Pushkarev V, Jaakkola JJ. Comparison of allergic diseases, symptoms and respiratory infections between Finnish and Russian school children. Eur J Epidemiol 2008: 23: 123–33.
- 27Hugg TT, Jaakkola MS, Ruotsalainen R, Pushkarev V, Jaakkola JJ. Exposure to animals and the risk of allergic asthma: a population-based cross-sectional study in Finnish and Russian children. Environ Health 2008: 7: 28.
- 28Hugg TT, Jaakkola MS, Ruotsalainen RO, Pushkarev VJ, Jaakkola JJ. Parental smoking behaviour and effects of tobacco smoke on children's health in Finland and Russia. Eur J Pub Health 2008: 18: 55–62.
- 29Linnakoski R, de Beer ZW, Rousi M, Niemela P, Pappinen A, Wingfield MJ. Fungi, including Ophiostoma karelicum sp. nov., associated with Scolytus ratzeburgi infesting birch in Finland and Russia. Mycol Res 2008: 112: 1475–88.
- 30Paalanen L, Prattala R, Alfthan G, Salminen I, Laatikainen T. Vegetable and fruit consumption, education and plasma vitamin C concentration in Russian and Finnish Karelia, 1992–2002. Public Health Nutr 2014: 17: 2278–86.
- 31Paalanen L, Prattala R, Laatikainen T. Contribution of education level and dairy fat sources to serum cholesterol in Russian and Finnish Karelia: results from four cross-sectional risk factor surveys in 1992–2007. BMC public health 2012: 12: 910.
- 32Paalanen L, Prattala R, Palosuo H, Helakorpi S, Laatikainen T. Socio-economic differences in the use of dairy fat in Russian and Finnish Karelia, 1994–2004. Int J Public Health 2010: 55: 325–37.
- 33Paalanen L, Prattala R, Palosuo H, Laatikainen T. Socio-economic differences in the consumption of vegetables, fruit and berries in Russian and Finnish Karelia: 1992-2007. Eur J Pub Health 2011: 21: 35–42.
- 34Munthe-Kaas MC, Torjussen TM, Gervin K, et al. CD14 polymorphisms and serum CD14 levels through childhood: a role for gene methylation? J Allergy Clin Immunol 2010: 125: 1361–8.
- 35Slaats GG, Reinius LE, Alm J, Kere J, Scheynius A, Joerink M. DNA methylation levels within the CD14 promoter region are lower in placentas of mothers living on a farm. Allergy 2012: 67: 895–903.
- 36Zhang S, Barros SP, Moretti AJ, et al. Epigenetic regulation of TNFA expression in periodontal disease. J Periodontol 2013: 84: 1606–16.
- 37Hanski I, von Hertzen L, Fyhrquist N, et al. Environmental biodiversity, human microbiota, and allergy are interrelated. Proc Natl Acad Sci USA 2012: 109: 8334–9.
- 38von Hertzen L, Beutler B, Bienenstock J, et al. Helsinki alert of biodiversity and health. Ann Med 2015: 47: 218–25.