The IL12B gene is associated with asthma.
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.
Channing Laboratory, Brigham and Women's Hospital, Department of Anesthesia, Children's Hospital, and Harvard Medical School, Boston, MA, USA. adrienne.randolph@tch.harvard.edu
Adrienne G
AG
Randolph
Christoph
C
Lange
Edwin K
EK
Silverman
Ross
R
Lazarus
Eric S
ES
Silverman
Benjamin
B
Raby
Alison
A
Brown
Al
A
Ozonoff
Brent
B
Richter
Scott T
ST
Weiss
D000328:Adult; D001249:Asthma / Q000235:genetics*; D002648:Child; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D018664:Interleukin-12 / Q000235:genetics*; D053762:Interleukin-12 Subunit p40; D015810:Linkage Disequilibrium; D008297:Male; D010375:Pedigree; D011110:Polymorphism, Genetic; D044465:White People / Q000235:genetics
C500879:IL12B protein, human; D053762:Interleukin-12 Subunit p40; D018664:Interleukin-12