Association of a haplotype block spanning SDAD1 gene and CXC chemokine genes with allergic rhinitis.
BACKGROUND
Seasonal allergic rhinitis (SAR) is a common allergic disorder characterized by episodes of sneezing, rhinorrhea, and swelling of the nasal mucosa. Although the pathogenesis of SAR remains unclear, there does appear to be a genetic predisposition to development of SAR. We previously identified regions of chromosomes 1p, 4q, and 9q linked to SAR in 48 families (188 members) identified through children with SAR against orchard grass pollens.


OBJECTIVE
The aim of the current study was to identify susceptibility genes for SAR on 4q.


METHODS
We screened for markers associated with SAR on 4q with 17 microsatellite markers and then for mutations in 11 genes. We genotyped 44 single nucleotide polymorphisms (SNPs) in 48 SAR families and performed haplotype-based haplotype relative risk statistics implemented in the UNPHASED program. We also examined expression of genes with human multiple tissue and immune system cDNA panels.


RESULTS
We found that 1 microsatellite marker, D4S3042, was associated with SAR (P = .034). The haplotype-based haplotype relative risk approach revealed that SNPs in SDA1 domain containing 1; chemokine, CXC motif, ligand (CXCL)-9; CXCL10; and CXCL11 were associated with SAR (P = .001-.04). These SNPs made up a haplotype block, and the most common haplotype of this block was transmitted preferentially to affected offspring (P = .002).


CONCLUSIONS
Our results suggests that genetic variations in a haplotype block spanning the SDA1 domain containing 1 and CXC chemokine genes on 4q21 may contribute to development of SAR in the Japanese population.
Zhang
Jian
J
Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba City, Ibaraki, Japan.
Noguchi
Emiko
E
Migita
Ohsuke
O
Yokouchi
Yukako
Y
Nakayama
Junko
J
Shibasaki
Masanao
M
Arinami
Tadao
T
D000293:Adolescent; D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000276:immunology; D019743:Chemokines, CXC / Q000235:genetics* / Q000276:immunology; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D006255:Rhinitis, Allergic, Seasonal / Q000235:genetics* / Q000276:immunology
D018797:Cell Cycle Proteins; D019743:Chemokines, CXC; D009687:Nuclear Proteins; C490621:SDAD1 protein, human