Lack of association of TIM3 polymorphisms and allergic phenotypes.
BACKGROUND
T-cell immunoglobulin mucin-3 (TIM3) is a TH1-specific type 1 membrane protein that regulates TH1 proliferation and the development of immunological tolerance. TIM3 and its genetic variants have been suggested to play a role in regulating allergic diseases. Polymorphisms in the TIM3 promoter region have been reported to be associated with allergic phenotypes in several populations. The aims of this study were to examine whether genetic variation in the promoter region of TIM3 influenced transcription of the gene and risk for allergic phenotypes.


METHODS
We performed 5' rapid amplification of cDNA ends and reverse transcription-polymerase chain reaction. We screened for polymorphisms in the promoter region. Deletion analysis was used to localize the promoter region of TIM3. Genotyping was performed by TaqMan assays in three asthma/allergy population samples.


RESULTS
We found two regions with promoter activity in TIM3. One region was from -214 bp to +58 bp and the other from -1.6 kb to -914 bp relative to the transcription start site. None of the single nucleotide polymorphisms (SNPs) or haplotypes affected the transcriptional activity in reporter gene assays. No association between the SNPs and any phenotype was observed in the study cohorts.


CONCLUSIONS
Our findings indicate that SNPs and haplotypes in the TIM3 promoter region do not have a functional effect in vitro and are not associated with allergic diseases. These data suggest that polymorphisms in the TIM3 promoter region are unlikely to play an important role in susceptibility to allergic diseases.
Zhang
Jian
J
James Hogg iCAPTURE Center for Cardiovascular and Pulmonary Research, St, Paul's Hospital, Vancouver, BC, Canada. zjs015195@yahoo.com
Daley
Denise
D
Akhabir
Loubna
L
Stefanowicz
Dorota
D
Chan-Yeung
Moira
M
Becker
Allan B
AB
Laprise
Catherine
C
Paré
Peter D
PD
Sandford
Andrew J
AJ
D024506:5' Flanking Region / Q000235:genetics; D000483:Alleles; D001249:Asthma / Q000235:genetics*; D044383:Black People; D002170:Canada; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D005838:Genotype; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D044465:White People
C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins