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Association between IL12B polymorphisms and tuberculosis risk: a meta-analysis.

Guoyuan Liu1, Guanghua Li2, Ying Xu3

  • 1The State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200433, China; Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China.

Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases
|December 25, 2013
PubMed
Summary

This meta-analysis found that the IL12B 3' UTR C allele may increase tuberculosis risk in Caucasians, but not in Asians or Africans. Ethnicity influences the impact of IL12B gene variations on TB susceptibility.

Keywords:
IL12B 3′ UTRIL12B promoterMeta-analysisPolymorphismTuberculosis

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Area of Science:

  • Immunogenetics
  • Human Genetics
  • Molecular Epidemiology

Background:

  • The interleukin (IL)-12B gene encodes a subunit common to IL-12 and IL-23, crucial for T helper cell type 1 (TH1) immune responses.
  • Polymorphisms in the IL12B 3' UTR and promoter regions have been linked to IL-12 p40 production and tuberculosis (TB) susceptibility, though findings are conflicting.

Purpose of the Study:

  • To conduct a meta-analysis to precisely estimate the association between IL12B polymorphisms (3' UTR and promoter) and TB risk.
  • To investigate the influence of ethnicity on the relationship between IL12B gene variants and TB susceptibility.

Main Methods:

  • Meta-analysis of 11 case-control studies for the IL12B 3' UTR polymorphism (2897 cases/2653 controls) and 4 studies for the IL12B promoter polymorphism (1037 cases/1126 controls).
  • Crude odds ratios (OR) with 95% confidence intervals (CI) were calculated using fixed- and random-effects models.
  • Stratified analyses were performed based on ethnicity.

Main Results:

  • No significant overall association was found for the IL12B 3' UTR variant in genotypic or allelic tests.
  • A significant association was observed in Caucasians for the IL12B 3' UTR variant in the dominant model (AC+CC vs. AA: OR=0.69, 95% CI: 0.51-0.93) and allelic contrast (C allele: OR=0.74, 95% CI: 0.58-0.95).
  • No significant associations were detected for the IL12B promoter variant or in Asian or African populations for the 3' UTR variant.

Conclusions:

  • The C allele of the IL12B 3' UTR may represent a TB risk factor specifically in Caucasian populations.
  • The effect of IL12B polymorphisms on TB risk appears to be ethnicity-dependent.
  • Further large-scale, ethnically diverse studies are needed to validate these findings.