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.
Randolph
Adrienne G
AG
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
Lange
Christoph
C
Silverman
Edwin K
EK
Lazarus
Ross
R
Silverman
Eric S
ES
Raby
Benjamin
B
Brown
Alison
A
Ozonoff
Al
A
Richter
Brent
B
Weiss
Scott T
ST
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