title: Interleukin-6 gene variation in Spanish patients with immunoglobulin-A deficiency.
abstract: Selective immunoglobulin-A deficiency (IgAD) is the most common immunodeficiency in Caucasian populations. Genetic factors are important in its etiology; however human leukocyte antigen (HLA) genes, which explain 40% of the genetic risk for IgAD, are the only susceptibility factors commonly agreed upon at this time. Because interleukin-6 (IL-6) plays an important role in B-lymphocyte differentiation from plasma cells, we aimed to address the IL-6 genetic influence on IgAD susceptibility. We performed a case-control study that included 305 Caucasian Spanish IgAD patients and 529 ethnically matched healthy control subjects, as well as a familial study with 128 IgAD trios. We genotyped the functional promoter polymorphism -174G>C and nine additional single nucleotide polymorphisms. For the case-control analyses the chi(2) test or Fisher's exact test were used, and for the family study the transmission disequilibrium test was used. We observed an increased frequency of the -174C allele in IgAD patients (p = 0.005, odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.12-2.04) and a protective effect of the rs2069849_C allele (p = 0.007, odds ratio = 0.29, 95% CI = 0.09-0.76). In conclusion, we described for the first time an association between IL6 polymorphisms and IgAD. Although it is not clear which genetic variants are causing susceptibility/protection, this intriguing finding is remarkable because of the role of IL-6 in antibody production.
authors.affiliation: Department of Clinical Immunology, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: López-Mejías
authors.forename: Alfonso
authors.initials: A
authors.lastname: Martínez
authors.forename: Nadia
authors.initials: N
authors.lastname: Del Pozo
authors.forename: Miguel
authors.initials: M
authors.lastname: Fernández-Arquero
authors.forename: Antonio
authors.initials: A
authors.lastname: Ferreira
authors.forename: Elena
authors.initials: E
authors.lastname: Urcelay
authors.forename: Gumersindo
authors.initials: G
authors.lastname: Fontán
authors.forename: Emilio G
authors.initials: EG
authors.lastname: de la Concha
authors.forename: Concepción
authors.initials: C
authors.lastname: Núñez
mesh_terms: D016022:Case-Control Studies; D016001:Confidence Intervals; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D017098:IgA Deficiency / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D013030:Spain / Q000453:epidemiology; D044465:White People
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6