A functional polymorphism in the TIM-1 gene is associated with asthma in a Chinese Han population.
BACKGROUND
TIM-1, a member of the T cell immunoglobulin and mucin domain (TIM) gene family was implicated as an asthma susceptibility gene in previous studies. TIM-1 is selectively expressed on activated CD4+ T cells and its expression is sustained preferentially on T helper type 2 (Th2) cells, which suggests that TIM-1 is associated with T cell differentiation and the development of Th2-biased immune response.


METHODS
In order to evaluate the effects of the promoter polymorphism in the TIM-1 gene on asthma susceptibility in a Chinese Han population, 2 promoter polymorphisms, -416G>C and -1454G>A, from 2 alternative promoter regions, were genotyped in 409 unrelated asthma patients and 305 healthy controls by using polymerase chain reaction and restriction fragment length polymorphism. Also, we analyzed the functional significance of -416G>C using the luciferase reporter gene assay.


RESULTS
We found that -416G>C was associated with asthma susceptibility in our study population (chi2 = 9.88, p = 0.002, odds ratio 1.41, 95% confidence interval 1.14-1.75). No statistically significant difference in the distribution of genotype and allele frequency of the -1454G>A site was observed. The -416G>C substitution increased the transcriptional activity of the TIM-1 gene.


CONCLUSIONS
Our findings suggest that the -416G>C variation site in the human TIM-1 promoter region is associated with asthma susceptibility in a Chinese Han population.
Liu
Qiji
Q
Key Laboratory of Experimental Teratology, Ministry of Education, China, Institute of Medical Genetics, School of Medicine, Shandong University, Jinan, PR China.
Shang
Linshan
L
Li
Jisheng
J
Wang
Pin
P
Li
Huaichen
H
Wei
Chunhua
C
Gong
Yaoqin
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000235:genetics*; D002681:China; D005260:Female; D020022:Genetic Predisposition to Disease; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011991:Receptors, Virus / Q000235:genetics*
C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D008562:Membrane Glycoproteins; D011991:Receptors, Virus