title: Analysis of a functional BTNL2 polymorphism in type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosus.
abstract: The aim of this study was to test whether the functional variant rs2076530 of the BTNL2 gene confers susceptibility to the autoimmune diseases type 1 diabetes (T1D), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Our study populations consisted of 326 patients with T1D and 351 healthy subjects, 808 patients with RA and 1137 healthy controls, and 372 patients with SLE and 280 healthy controls. Genotyping of the BTNL2 gene rs2076530 polymorphism was performed by real-time polymerase chain reaction technology, using the TaqMan 5'-allele discrimination assay. We observed statistically significant differences in the distribution of BTNL2rs2076530 alleles between patients with T1D, RA, and SLE and healthy controls (p=0.0035, 0.000003, and 0.00002, respectively), but in two divergent ways: the G allele was associated with T1D and RA, and the A allele was associated with SLE. However, the polymorphism exhibited strong linkage disequilibrium with HLA DQB1-DRB1 haplotypes previously identified as predisposing to the diseases. When the BTNL2 polymorphism was tested conditional on HLA DQB1-DRB1haplotypes, the BTNL2 effect was no longer significant in all three study populations. The BTNL2 rs2076530 polymorphism is associated with T1D, RA, and SLE because of its strong linkage disequalibrium with predisposing HLA DQB1-DRB1 haplotypes in Caucasian populations.
authors.affiliation: Instituto de Biomedicina, CSIC, Granada, Spain.
authors.forename: Gisela
authors.initials: G
authors.lastname: Orozco
authors.forename: Peter
authors.initials: P
authors.lastname: Eerligh
authors.forename: Elena
authors.initials: E
authors.lastname: Sánchez
authors.forename: Sasha
authors.initials: S
authors.lastname: Zhernakova
authors.forename: Bart O
authors.initials: BO
authors.lastname: Roep
authors.forename: Miguel A
authors.initials: MA
authors.lastname: González-Gay
authors.forename: Miguel A
authors.initials: MA
authors.lastname: López-Nevot
authors.forename: Jose L
authors.initials: JL
authors.lastname: Callejas
authors.forename: Carmen
authors.initials: C
authors.lastname: Hidalgo
authors.forename: Dora
authors.initials: D
authors.lastname: Pascual-Salcedo
authors.forename: Alejandro
authors.initials: A
authors.lastname: Balsa
authors.forename: María F
authors.initials: MF
authors.lastname: González-Escribano
authors.forename: Bobby P C
authors.initials: BP
authors.lastname: Koeleman
authors.forename: Javier
authors.initials: J
authors.lastname: Martín
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics*; D000071797:Butyrophilins; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
chemical_list: C408263:BTNL2 protein, human; D000071797:Butyrophilins; D008562:Membrane Glycoproteins