The IL12B gene is associated with asthma

Am J Hum Genet. 2004 Oct;75(4):709-15. doi: 10.1086/424886. Epub 2004 Aug 20.

Abstract

The IL12B gene on chromosome 5q31-33 encodes the p40 subunit of interleukin 12, an immunomodulatory cytokine. To test the hypothesis that the IL12B gene contains polymorphisms associated with asthma, we genotyped six haplotype-tagging polymorphisms in the IL12B gene, both in 708 children enrolled in the Childhood Asthma Management Program (CAMP) and in their parents. Using the family-based association test (FBAT) program and its haplotype (HBAT) and phenotype (PBAT) options, we tested each polymorphism and haplotype for association with asthma and asthma-related phenotypes. We tested positive associations for replication in a case-control study comparing 177 adult moderate-to-severe asthmatics with 177 nonasthmatic controls. In whites in the CAMP cohort, the A allele of the IL12B G4237A polymorphism was undertransmitted to asthmatic children (P=.0008, recessive model), the global test for haplotypes for affection status was positive (P=.009, multiallelic chi (2)), and two polymorphisms were associated with different atopy phenotypes. In addition, we found a strong association between the IL12B_4237 and IL12B_6402 polymorphisms and an asthma-severity phenotype in whites, which we also found in the independent population of white adult asthmatics. IL12B may be an important asthma gene.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Asthma / genetics*
  • Child
  • Chromosomes, Human, Pair 5 / genetics*
  • Cohort Studies
  • European Continental Ancestry Group / genetics
  • Female
  • Genotype
  • Haplotypes / genetics
  • Humans
  • Inheritance Patterns / genetics
  • Interleukin-12 / genetics*
  • Interleukin-12 Subunit p40
  • Linkage Disequilibrium
  • Male
  • Pedigree
  • Polymorphism, Genetic*

Substances

  • IL12B protein, human
  • Interleukin-12 Subunit p40
  • Interleukin-12