title: Polymorphisms in the IL2, IL2RA and IL2RB genes in multiple sclerosis risk.
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 (P(Mantel-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 (P(M-H)=0.07, OR(M-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.
authors.affiliation: Immunology Department, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: María L
authors.initials: ML
authors.lastname: Cavanillas
authors.forename: Antonio
authors.initials: A
authors.lastname: Alcina
authors.forename: Concepción
authors.initials: C
authors.lastname: Núñez
authors.forename: Virginia
authors.initials: V
authors.lastname: de las Heras
authors.forename: Miguel
authors.initials: M
authors.lastname: Fernández-Arquero
authors.forename: Manuel
authors.initials: M
authors.lastname: Bartolomé
authors.forename: Emilio G
authors.initials: EG
authors.lastname: de la Concha
authors.forename: Oscar
authors.initials: O
authors.lastname: Fernández
authors.forename: Rafael
authors.initials: R
authors.lastname: Arroyo
authors.forename: Fuencisla
authors.initials: F
authors.lastname: Matesanz
authors.forename: Elena
authors.initials: E
authors.lastname: Urcelay
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D015331:Cohort Studies; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics*; D053646:Interleukin-2 Receptor beta Subunit / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics; D016015:Logistic Models; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013030:Spain; D055815:Young Adult
chemical_list: D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D053646:Interleukin-2 Receptor beta Subunit