Abstract
Interleukin (IL)-2/IL-2R signalling promotes proliferation and survival of activated T cells and has an essential non-redundant role in the production of regulatory T cells. Associations with different autoimmune diseases of polymorphisms in a linkage disequilibrium block in which the IL2/IL21 genes map (4q27), and also in genes encoding the IL2RA and IL2RB subunits (located in 10p15 and 22q13, respectively), were identified through genome-wide studies. Polymorphisms in these three genes were studied in 430 multiple sclerosis (MS) patients and in 550 ethnically matched controls from Madrid (Spain). Replication and meta-analysis with results from an independent cohort of 771 MS patients and 759 controls from Andalucía (Spain) confirmed the association of polymorphisms in the IL2RA gene (PMantel–Haenszel, odds ratio (OR)M–H (95% confidence interval, CI) for rs2104286: 0.0001, 0.75 (0.65–0.87); for rs11594656/rs35285258: 0.004, 1.19 (1.06–1.34); for rs41295061: 0.03, 0.77 (0.60–0.98)); showed a trend for association of the IL2/IL21 rs6822844 (PM–H=0.07, ORM–H (95% CI)=0.86 (0.73–1.01)), but did not corroborate the association for IL2RB. Regression analyses of the combined Spanish cohort revealed the independence of two IL2RA association signals: rs2104286 and rs11594656/rs35285258. The relevant role of the IL2RA gene on MS susceptibility adds support to its common effect on autoimmune risk and the suggestive association of IL2/IL21 warrants further investigation.
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Acknowledgements
We thank Carmen Martínez and M Angel García for their skilful technical assistance. Concepción Núñez holds a research contract from Fondo Investigaciones Sanitarias (CA06/0163) and Elena Urcelay works for the Fundación para la Investigación Biomédica-Hospital Clínico San Carlos. This study was supported by grants from: Alfonso Martín Escudero Foundation and Fondo Investigaciones Sanitarias FIS PI07/0353, FIS PI07/0369, PI08/1636 and Plan Nacional PN-SAF2006-02023.
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Cavanillas, M., Alcina, A., Núñez, C. et al. Polymorphisms in the IL2, IL2RA and IL2RB genes in multiple sclerosis risk. Eur J Hum Genet 18, 794–799 (2010). https://doi.org/10.1038/ejhg.2010.15
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DOI: https://doi.org/10.1038/ejhg.2010.15
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