Evaluation of cytokine genetic polymorphisms in adult patients with common variable immunodeficiency: A single-center study.
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.
Institute of Human Genetics, School of Medicine University of Belgrade, Visegradska 26, 11000 Belgrade, Serbia. Electronic address: dijana.perovic@mfub.bg.ac.rs.
Dijana
D
Perovic
Institute of Microbiology and Immunology, School of Medicine University of Belgrade, Pasterova 2, 11000 Belgrade, Serbia.
Vladimir
V
Perovic
Institute of Microbiology and Immunology, School of Medicine University of Belgrade, Pasterova 2, 11000 Belgrade, Serbia.
Vera
V
Pravica
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.
Branka
B
Bonaci-Nikolic
Clinic of Allergy and Immunology, Clinical Center of Serbia, Koste Todorovica 2, 11000 Belgrade, Serbia.
Radovan
R
Mijanovic
Institute of Human Genetics, School of Medicine University of Belgrade, Visegradska 26, 11000 Belgrade, Serbia.
Vera
V
Bunjevacki
D000328:Adult; D017074:Common Variable Immunodeficiency / Q000235:genetics* / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics*; D016753:Interleukin-10 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D013163:Splenomegaly / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma
Common variable immunodeficiency; Cytokine polymorphism; Interferon gamma; Interleukin 10; Interleukin 6; Tumor necrosis factor