Interleukin (IL)-12, IL-2, interferon-gamma gene polymorphisms in subacute sclerosing panencephalitis patients
Vuslat Yilmaz1, Veysi Demirbilek, Candan Gürses
1Department of Physiology, Istanbul Medical Faculty, Istanbul, Turkey.
Abstract:
Mutated measles virus variants have been claimed as the causing agent for subacute sclerosing panencephalitis (SSPE) developing several years after the recovery from measles infection. However, immune dysfunction may be considered related to a genetic susceptibility to this rare disease. Interleukin (IL)-2 -330 (rs2069 762) and +160 (rs2069 763), IL-12 p40 3' UTR (rs3213113), and interferon (IFN)-gamma +874 (rs2430561) polymorphisms are screened by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and PCR-sequence-specific priming (SSP) methods in 87 SSPE patients and 106 healthy controls (HCs) as candidate genes of susceptibility. The distribution of the IL12B genotypes (rs3213113) showed a trend for a significant difference (P = .053). The frequency of IL12B C allele (P = .04, OR: 1.6) and CC genotype (P = .03, OR: 3.2) were both higher in SSPE patients than in HC. The IL2 -330 genotypes revealed lower frequencies of GG genotype (P = .03, OR: 0.4) as well as G allele (P = .02, OR: 0.6) in SSPE. IL2 -330+160 TG haplotype was more frequent in patients (P = .005, OR: 1.8), whereas GG haplotype was less frequent, compared to controls (P = .02, OR: 0.6). IFNG +874 polymorphism revealed no difference. These findings implicate possible effects of genetic polymorphisms in the susceptibility to SSPE, which need to be confirmed in other populations.
Insights
Genetic variations in Interleukin-12 (IL-12) and Interleukin-2 (IL-2) genes may increase susceptibility to subacute sclerosing panencephalitis (SSPE). These findings suggest a genetic component to SSPE risk beyond measles virus infection alone.
Area of Science:
- Immunogenetics
- Neuroscience
- Viral pathogenesis
Background:
- Subacute sclerosing panencephalitis (SSPE) is a rare, fatal neurological disease that develops years after measles infection.
- While measles virus is implicated, genetic susceptibility and immune dysfunction are suspected contributing factors to SSPE development.
- Specific cytokine gene polymorphisms, including those for Interleukin-2 (IL-2) and Interleukin-12 (IL-12), are investigated as potential markers for SSPE susceptibility.
Purpose of the Study:
- To investigate the association between polymorphisms in IL-2, IL-12B, and Interferon-gamma (IFN-gamma) genes and susceptibility to SSPE.
- To identify specific genetic variants that may confer increased risk for developing SSPE after measles infection.
Main Methods:
- Genotyping of IL-2 (-330 and +160), IL-12B (3' UTR), and IFN-gamma (+874) polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and PCR-sequence-specific priming (SSP).
- Comparison of genotype and allele frequencies between 87 SSPE patients and 106 healthy controls (HCs).
Main Results:
- The IL-12B C allele and CC genotype were significantly more frequent in SSPE patients compared to HCs (P = .04, P = .03).
- The IL-2 GG genotype and G allele were less frequent in SSPE patients (P = .03, P = .02).
- The IL-2 TG haplotype was more frequent in SSPE patients, while the GG haplotype was less frequent (P = .005, P = .02). No significant difference was observed for IFNG +874.
Conclusions:
- Genetic polymorphisms in IL-12B and IL-2 are associated with susceptibility to SSPE.
- These findings suggest that genetic factors play a role in the pathogenesis of SSPE, potentially influencing immune responses to measles virus.
- Further studies in diverse populations are needed to confirm these genetic associations with SSPE risk.
