title: Study of polymorphisms in 4q27, 10p15, and 22q13 regions in autoantibodies stratified type 1 diabetes patients.
abstract: Type 1 diabetes (T1D) is a multifactorial disease mainly associated with the human leukocyte antigen region. Previous studies suggested the association of interleukin-2 (IL2) gene polymorphisms and its alpha- and beta-chain receptor (IL2RA and IL2RB) variants with different autoimmune diseases such as T1D, celiac disease, multiple sclerosis, and rheumatoid arthritis. All T1D studies were conducted in diabetic patients younger than 17 years at diagnosis. The aim of our study was to replicate these associations not only in pediatric patients, but also in individuals with late onset. We performed a genetic association study of chromosomal regions 4q27, 10p15, and 22q13 containing the IL2, IL2RA, and IL2RB genes in 445 T1D subjects and 828 healthy controls. Seven single nucleotide polymorphisms (SNPs) were selected, previously described as genetic factors related to several autoimmune diseases, and were analyzed by TaqMan assays. The reported association with T1D patients of the IL2RA-rs41295061 located in the 10p15 region was replicated and our data suggest a trend of association of the polymorphisms IL2-rs17388568 and IL2-rs6822844 in 4q27. The effect of these markers was independent of the age at disease onset. Furthermore, the polymorphisms studied in 4q27 were not dependent on the presence of autoantibodies; however, the effect of the associated SNP in 10p15 (IL2RA-rs41295061) was specific of patients sera positive for diabetes antibodies. In conclusion, our results seem to indicate that late-onset and young T1D patients share most genetic factors located in the studied regions, but some markers could correlate with the presence of T1D specific autoantibodies.
authors.affiliation: Immunology Department, Instituto de Investigación Sanitaria San Carlos, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Espino-Paisán
authors.forename: Hermenegildo
authors.initials: H
authors.lastname: De La Calle
authors.forename: Miguel
authors.initials: M
authors.lastname: Fernández-Arquero
authors.forename: M Angeles
authors.initials: MA
authors.lastname: Figueredo
authors.forename: Emilio G
authors.initials: EG
authors.lastname: De La Concha
authors.forename: Elena
authors.initials: E
authors.lastname: Urcelay
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Santiago
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000483:Alleles; D001323:Autoantibodies / Q000276:immunology*; D002879:Chromosomes, Human, Pair 10; D002892:Chromosomes, Human, Pair 22; D002894:Chromosomes, Human, Pair 4; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D005260:Female; D023061:Gene Order; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics; D053646:Interleukin-2 Receptor beta Subunit / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D053646:Interleukin-2 Receptor beta Subunit