title: Association of an NKG2D gene variant with systemic lupus erythematosus in two populations.
abstract: NKG2D, involved in T-cell activation and viral defense, shows a single-nucleotide polymorphism (SNP) in the transmembrane region, characterized by a substitution of alanine with threonine. We examined the association of systemic lupus erythematosus (SLE) with one of the NKG2D gene variants. We also studied the functional impact of that allele in SLE. Restriction fragment length polymorphism/polymerase chain reaction specific for the SNP rs2255336 G--> A was performed with 247 German SLE patients and 447 controls and with 284 Spanish SLE patients and 180 controls. NKG2D expression on peripheral blood lymphocytes of SLE patients was analyzed via fluorescence activated cell sorter. In addition, proliferation assays were performed. We found that the NKG2D alanine/alanine (G/G) gene variant was significantly associated with SLE in the German cohort (70.4% vs 60.8% controls; p = 0.0027) and almost significantly in the Spanish cohort (66.2% vs 62.2% controls; p = 0.054). In a pooled analysis, the prevalence of G/G was 68.2% in SLE versus 61.2% in the controls (p = 0.0024). There were no significant differences in the expression levels of NKG2D on peripheral blood lymphocytes of the different genotypes. A comparison of the coreceptor activity of the genotypes in response to CD3 and NKG2D antibodies revealed a trend toward higher proliferation in the A/A genotype. In conclusion, based on our study results, SLE is associated with the SNP rs2255336 of NKG2D.
authors.affiliation: Clinic for Immunology and Rheumatology, Hannover Medical School, Hannover, Germany. Gamze_Kabalak@gmx.de
authors.forename: Gamze
authors.initials: G
authors.lastname: Kabalak
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Thomas
authors.forename: Javier
authors.initials: J
authors.lastname: Martin
authors.forename: Noberto
authors.initials: N
authors.lastname: Ortego-Centeno
authors.forename: Juan
authors.initials: J
authors.lastname: Jimenez-Alonso
authors.forename: Enrique
authors.initials: E
authors.lastname: de Ramón
authors.forename: Sabine
authors.initials: S
authors.lastname: Buyny
authors.forename: Sandra
authors.initials: S
authors.lastname: Hamsen
authors.forename: Wolfgang L
authors.initials: WL
authors.lastname: Gross
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schnarr
authors.forename: Henning
authors.initials: H
authors.lastname: Zeidler
authors.forename: Erika
authors.initials: E
authors.lastname: Gromnica-Ihle
authors.forename: Reinhold E
authors.initials: RE
authors.lastname: Schmidt
authors.forename: Torsten
authors.initials: T
authors.lastname: Witte
mesh_terms: D000483:Alleles; D049109:Cell Proliferation; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K