Interleukin-6 gene variation in Spanish patients with immunoglobulin-A deficiency

• Published in: Human immunology 2008-04, Vol.69 (4), p.301-305
• Main Authors: López-Mejías, Raquel, Martínez, Alfonso, del Pozo, Nadia, Fernández-Arquero, Miguel, Ferreira, Antonio, Urcelay, Elena, Fontán, Gumersindo, de la Concha, Emilio G, Núñez, Concepción
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Case-Control Studies; Confidence Intervals; Disease susceptibility; European Continental Ancestry Group; Gene Frequency; Genetic Predisposition to Disease; Haplotypes; Humans; IgA Deficiency - genetics; Interleukin-6; Interleukin-6 - genetics; Odds Ratio; Polymorphism; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Selective IgA deficiency; Spain - epidemiology
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2008.02.002

Summary 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 χ2 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.