Genetic impact of functional single nucleotide polymorphisms in the 3'-UTR region of the chemoattractant receptor expressed on Th2 cells (CRTH2) gene on asthma and atopy in a Japanese population.
BACKGROUND
The human chemoattractant receptor expressed on Th2 cells (CRTH2), the receptor for prostaglandin D2, induces cell migration in eosinophils, basophils, and Th2 cells. The gene encoding CRTH2 is located on chromosome 11q13. Several groups, including ours, have reported significant associations between this region and various traits associated with allergic diseases such as asthma and atopy. Two single nucleotide polymorphisms in the 3'-UTR of the CRTH2 gene (1544G-->C and 1651G-->A) are associated with the mRNA stability of the gene; they have also been associated with asthma in both African American and Chinese populations.


METHODS
Because CRTH2 is a biologically important candidate gene on chromosome 11q13, we conducted a case-control analysis using 787 Japanese subjects (384 asthmatics and 403 controls) to evaluate the genetic impact of the CRTH2 gene on asthma and asthma-related traits. Four polymorphisms [1544G-->C (rs11571288), 1651G-->A (rs545659), 11336T-->C (rs2074422), and 12375G-->T (rs561285)] were studied.


RESULTS
The allele, genotype, or haplotype frequencies for 2 functional polymorphisms in our Japanese population were significantly different from those in the Chinese or African American populations. No association was found between any polymorphisms or haplotypes in the CRTH2 gene and asthma, atopy, or total serum IgE levels in a Japanese population.


CONCLUSIONS
Our data failed to support previous associations of functional polymorphisms at the 3'-UTR of the CRTH2 gene implicated in asthma. We did show a significant difference in the allele and genotype frequencies as well as different haplotype frequencies among African American, Chinese, and Japanese populations, suggesting that the genetic impacts of these functional polymorphisms on asthma and asthma-related phenotypes may vary in different populations.
Maeda
Yukiko
Y
First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Hizawa
Nobuyuki
N
Takahashi
Daisuke
D
Fukui
Yoshinobu
Y
Konno
Satoshi
S
Nishimura
Masaharu
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000097:blood / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D004804:Eosinophils / Q000276:immunology; D005260:Female; D005541:Forced Expiratory Volume; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000097:blood / Q000235:genetics* / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D007564:Japan / Q000453:epidemiology; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011971:Receptors, Immunologic / Q000235:genetics*; D011982:Receptors, Prostaglandin / Q000235:genetics*; D020506:Untranslated Regions
D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D020506:Untranslated Regions; D007073:Immunoglobulin E; C036293:prostaglandin D2 receptor