The IL9R region contribution in asthma is supported by genetic association in an isolated population

Abstract

Interleukin 9 (IL9) is involved in mast cell maturation and the enhancement of IgE production by B cells. Furthermore, linkage data in human and mice have suggested that IL9 may contribute to asthma. Since our genetic analysis of the 5q cytokine cluster did not support a genetic role for the IL9 gene, we became interested in the IL9 receptor gene (IL9R) in the pseudoautosomal region. We genotyped markers sDF2 and sDF1 close to the IL9R gene among 289 affected and 368 family-based controls. The results were studied by using linkage, transmission disequilibrium, association and homozygosity analyses. Linkage analyses remained negative, presumably because of our low power for linkage study. However, all the other analyses yielded evidence that the IL9R gene region may have a role in the development of asthma. The sDF2*10 allele was more frequently transmitted than untransmitted to asthmatic offspring (34 vs 16, P 2 ≤ 0.01), and it was found homozygotic among asthma patients more often than expected (P simul2 = 0.009). Also, a specific X chromosomal haplotype, sDF2*10-sDF1*6 associated with asthma (40 vs 7, P 2 < 0.005, P simul1 = 0.04).

Profiling of genes expressed in peripheral blood mononuclear cells predicts glucocorticoid sensitivity in asthma patients

“…Several studies have reported association between asthma and the X chromosome (27)(28)(29). In our study, nearly 80% of the GC-R patients were females.…”

The Human Pseudoautosomal Region (PAR): Origin, Function and Future

“…The sDF2*10 allele of IL9R is more frequently transmitted than untransmitted to asthmatic offspring and the allele was found to be homozygous more often than expected in asthma patients [29]. Also, a specific X-chromosome haplotype (sDF2*10-sDF1*6) was found to be associated with asthma [29]. In support of the involvement of IL9R in allergic diseases, a specific IL9R haplotype appears to protect against wheezing in boys [30].…”

“…A role for IL9R in the development of asthma has been suggested [28,29]. The sDF2*10 allele of IL9R is more frequently transmitted than untransmitted to asthmatic offspring and the allele was found to be homozygous more often than expected in asthma patients [29]. Also, a specific X-chromosome haplotype (sDF2*10-sDF1*6) was found to be associated with asthma [29].…”

“…IL9R (also known as CD129) belongs to the hematopoietin receptor subfamily and PAR2 expresses this gene in both membrane-bound and soluble forms [27]. A role for IL9R in the development of asthma has been suggested [28,29]. The sDF2*10 allele of IL9R is more frequently transmitted than untransmitted to asthmatic offspring and the allele was found to be homozygous more often than expected in asthma patients [29].…”

Human Population Genetics: Lessons from Finland

“…For example, Laitinen et al (39) recruited asthma patients and their families from the Kainuu region for susceptibility gene studies. The origin of the subjects was verified from population registries, and several candidate gene regions were considered (25,39,40). Haplotype association analysis was employed in addition to genetic linkage analysis to increase power, and the investigators estimated that the study material would have allowed a good chance to identify an associated haplotype present in 15% of all patient chromosomes.…”