Allergic rhinitis – a total genome-scan for susceptibility genes suggests a locus on chromosome 4q24-q27

Abstract

Allergic rhinitis is a common disease of complex inheritance and is characterised by mucosal inflammation caused by allergen exposure. The genetics of closely related phenotypes such as asthma, atopy and to some extend atopic dermatitis has attracted attention in recent years. Genetic reports of allergic rhinitis on the contrary have as yet been most sparse. To identify candidate regions holding genes for allergic rhinitis we performed a total genome-scan on affected sib-pair families. From 100 Danish sib-pair families selected for allergy, families containing sib-pairs matching a phenotype definition of both clinical allergic rhinitis and confirmed specific allergy were chosen. Thirty-three affected sib-pair families qualified for the scan that was undertaken using 446 microsatellite markers. Non-parametric linkage results were obtained from MAPMAKER/SIBS computer program. The study revealed one major candidate region on chromosome 4q24-q27 (LOD=2.83) and eight minor candidate regions 2q12-q33, 3q13, 4p15-q12, 5q13-q15, 6p24-p23, 12p13, 22q13, and Xp21 (LOD=1.04 ± 1.63) likely to contain susceptibility genes for allergic rhinitis. Our findings did not support a previous report of linkage of allergic rhinitis to chromosome 12q14-q24 but they added positive evidence to the asthma and atopy candidate regions 2q33 and 6p23. Further identification of the specific genes involved in allergic rhinitis will give opportunities for improved diagnosis and treatment. European Journal of Human Genetics (2001) 9, 945 ± 952.

Genome screen in the French EGEA study: detection of linked regions shared or not shared by allergic rhinitis and asthma

“…13 The linkage peak in the 2q32 region observed here for AR is about 40 cM apart from the linked region indicated in the Danish scan. 12 The other regions, 1p36 and 4q13, detected in the Japanese genome scan and 4q24-27 detected in the Danish screen were not replicated here. Lack of replication between the results of the French, Danish and the Japanese studies may be explained by either statistical issues (spurious detection of linkage, due to multiple tests, and/or lack of power) or by the heterogeneity between samples in terms of the phenotype definition (based only on questionnaire in the EGEA and Japanese studies and based on both questionnaire and clinical examination in the Danish study) and/or by the mode of ascertainment of the families.…”

“…However, accumulating indication for linkage across studies may be more important than unreplicated high linkage peaks to identify regions of interest. The present study is the third published genome scan of AR after one screen conducted in a Danish sample 12 and another one in a Japanese one. 13 The 9q22-q34 region detected for potential linkage to AR in our sample was also reported in the Japanese scan.…”

“…These genome screens have led to identification of four genes by positional cloning: ADAM33 associated with asthma and BHR located on chromosome 20, 8 PHF11 associated with IgE levels and severe asthma on chromosome 13, 9 DPP10 associated with asthma on chromosome 2 10 and GPRA associated with high serum IgE or asthma on chromosome 7p. 11 In contrast, only two genome-wide searches 12,13 have been recently conducted for AR that showed potential linkage to the following chromosomal regions: 4q24-q27 in a Danish sample of 33 families 12 and 1p36, 4q13 and 9q34 in a Japanese sample of 48 families. 13 No linkage region was common to these two studies and only the 1p36 region had been previously reported for asthma.…”

Sex-specific effect of IL9 polymorphisms on lung function and polysensitization

“…5,15 Our other three regions of linkage are new regions, as only the 4q24 region has been reported once to be linked to allergic rhinitis. 16 However, these regions contain several candidate genes potentially involved in asthma or asthma-related phenotypes. 5,15,17 Following these linkage findings, bivariate association analysis of SPTQ and FEV 1 /H 2 with markers in 5q31 showed significant association with two SNPs, rs2069885 and rs2069882, within IL9 gene in males.…”

Family based association analysis of the IL2 and IL15 genes in allergic disorders

“…We have previously reported linkage of allergic rhinitis to chromosome 4q24 -27 in a genome scan of Danish sib-pair families (LOD score 3.26). 10 In a recent fine-mapping study, we found evidence of linkage of additional atopy phenotypes to the same region, including increased serum levels of specific IgE (positive RAST test) and asthma. 11 The IL2 gene is located at 4q27 and consists of four exons.…”