Evaluation of cytokine genetic polymorphisms in adult patients with common variable immunodeficiency: A single-center study

Dijana Perovic; Vladimir Perovic; Vera Pravica; Branka Bonaci-Nikolic; Radovan Mijanovic; Vera Bunjevacki

doi:10.1016/j.imlet.2016.05.005

Evaluation of cytokine genetic polymorphisms in adult patients with common variable immunodeficiency: A single-center study

Immunol Lett. 2016 Aug:176:97-104. doi: 10.1016/j.imlet.2016.05.005. Epub 2016 Jun 8.

Authors

Dijana Perovic¹, Vladimir Perovic², Vera Pravica², Branka Bonaci-Nikolic³, Radovan Mijanovic⁴, Vera Bunjevacki⁵

Affiliations

¹ Institute of Human Genetics, School of Medicine University of Belgrade, Visegradska 26, 11000 Belgrade, Serbia. Electronic address: dijana.perovic@mfub.bg.ac.rs.
² Institute of Microbiology and Immunology, School of Medicine University of Belgrade, Pasterova 2, 11000 Belgrade, Serbia.
³ Department of Internal Medicine, School of Medicine University of Belgrade, Dr Subotica 8, 11000 Belgrade, Serbia; Clinic of Allergy and Immunology, Clinical Center of Serbia, Koste Todorovica 2, 11000 Belgrade, Serbia.
⁴ Clinic of Allergy and Immunology, Clinical Center of Serbia, Koste Todorovica 2, 11000 Belgrade, Serbia.
⁵ Institute of Human Genetics, School of Medicine University of Belgrade, Visegradska 26, 11000 Belgrade, Serbia.

PMID: 27288995
DOI: 10.1016/j.imlet.2016.05.005

Abstract

Common variable immunodeficiency (CVID) is a heterogeneous disease characterized by impaired B-cell differentiation and maturation accompanied with the defective antibody production. Several investigators addressed the possibility that disturbed cytokine production of TNF, IL-6, IFN-γ and IL-10, among a variety of others, may be implicated in CVID. The aim of this study was to test the hypothesis that genetic polymorphisms involving TNF (-308G/A), IFNG (+874 T/A), IL10 (-1082G/A, -819T/C and -592A/C), and IL6 (-174G/C) cytokine genes might contribute to susceptibility to CVID. Thirty five patients with CVID and 250 healthy controls were genotyped for indicated single nucleotide polymorphisms (SNP) in TNF, IL6, IFNG and IL10 using Taqman-based assays. CVID patients had significantly higher frequency of TNF A allele and AA genotype than in healthy subjects (p=0.006; OR=2.27; 95%CI=1.24-4.17 and p=0.038, OR=15.64; 95%CI=1.38-177.20, respectively). In addition, the frequency of GG genotype was significantly higher in healthy controls than in patient group (p=0.019, OR=0.43, 95%CI=0.21-0.89). Genetic analysis of IL6 SNP showed that allele G confers increased risk for CVID (p=0.037, OR=1.78, 95% CI=1.03-3.08) while IFNG allele T was associated with splenomegaly in CVID (p=0.032; OR=2.86; 95% CI=1.08-7.56). We observed no association between genotypes, alleles and haplotypes of IL-10 gene and CVID or its clinical complications. In conclusion, our results indicated association between CVID and cytokine gene polymorphisms -308G/A TNF and -174G/C IL6. In addition, we demonstrated that splenomegaly, one of the most common complications in this disease, is associated with +874T/A IFNG polymorphism. These findings add further support to the notion that cytokines may play significant role in pathogenesis of this primary antibody deficiency. However, further investigation that would involve a larger study group of CVID patients is warranted to confirm our findings.

Keywords: Common variable immunodeficiency; Cytokine polymorphism; Interferon gamma; Interleukin 10; Interleukin 6; Tumor necrosis factor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Common Variable Immunodeficiency / genetics*
Common Variable Immunodeficiency / immunology
Female
Gene Frequency
Genetic Association Studies
Genetic Predisposition to Disease
Genotype
Humans
Interferon-gamma / genetics*
Interleukin-10 / genetics
Interleukin-6 / genetics*
Male
Polymorphism, Single Nucleotide
Splenomegaly / genetics*
Tumor Necrosis Factor-alpha / genetics*

Substances

Interleukin-6
Tumor Necrosis Factor-alpha
Interleukin-10
Interferon-gamma