Rheumatology International

, Volume 32, Issue 1, pp 53–59 | Cite as

Functional genetic polymorphisms in interleukin-12B gene in association with systemic lupus erythematosus

  • Lyuba D. MitevaEmail author
  • Irena M. Manolova
  • Mariana G. Ivanova
  • Rasho K. Rashkov
  • Rumen M. Stoilov
  • Maya V. Gulubova
  • Spaska A. Stanilova
Original Article


Genetic polymorphisms in cytokine genes, which influence gene expression, may have an important impact on SLE susceptibility and severity. The aim of this study was to examine the possible influence of two functional polymorphisms in cis-regulatory regions of IL12B gene in the susceptibility and clinical symptoms of SLE in Bulgarian patients. Female SLE patients (n = 141) and 124 healthy women were included in the study. Genotyping for the IL12B A/C polymorphism in 3′UTR was performed by restriction fragment length polymorphisms PCR assay and for the IL12Bpro polymorphism by allele-specific PCR. Genotype-22 of IL12Bpro polymorphism was overrepresented among women with SLE (28 vs. 17%; OR = 1.875; 95% CI: 1.037 ÷ 3.390; P = 0.037). Respectively, a higher frequency of allele-2 was found in patients than in controls (51% vs. 40%; OR = 1.566; 95% CI: 1.110 ÷ 2.210; P = 0.011). Also, we found significantly elevated frequency of genotype-22 of IL12Bpro polymorphism among SLE patients who were simultaneously carrier of genotype-AA of SNP in 3′UTR. Women with both homozygous genotypes, genotype-AA of SNP in 3′UTR and genotype-22 of IL12Bpro polymorphism, had a 2.1-fold significantly elevated risk for SLE development. The carrying of genotype-11 of IL12Bpro polymorphism was positively associated with hematological and neuropsychiatric manifestations of SLE. We have provided evidence that the IL12Bpro polymorphism was associated with SLE development among Bulgarian women. Although a strong individual effect of SNP in 3′UTR of IL12B was not detected, we found that genotype-22 of IL12Bpro was predominantly combined with genotype-AA of SNP in 3′UTR among SLE patients and this combination elevates the risk of SLE.


IL12B Gene polymorphism Systemic lupus erythematosus 


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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Lyuba D. Miteva
    • 1
    Email author
  • Irena M. Manolova
    • 2
  • Mariana G. Ivanova
    • 3
  • Rasho K. Rashkov
    • 3
  • Rumen M. Stoilov
    • 3
  • Maya V. Gulubova
    • 4
  • Spaska A. Stanilova
    • 1
  1. 1.Medical Faculty, Department of Molecular Biology, Immunology and Medical GeneticsTrakia UniversityStara ZagoraBulgaria
  2. 2.Medical Faculty, Laboratory of Clinical Immunology, University HospitalTrakia UniversityStara ZagoraBulgaria
  3. 3.Clinic of RheumatologyUniversity Hospital, Medical AcademySofiaBulgaria
  4. 4.Medical Faculty, Department of General and Clinical PathologyTrakia UniversityStara ZagoraBulgaria

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