The RANTES promoter polymorphism: a genetic risk factor for near-fatal asthma in Chinese children.
BACKGROUND
RANTES promoter polymorphisms were found associated with asthma/atopy in some studies but not others, possibly reflecting the genetic heterogeneity among different ethnicities and different asthma severity.


OBJECTIVE
The purpose of this investigation was to test the genetic association between the RANTES -28C/G and -403G/A polymorphisms and asthma/atopy in a cohort of Chinese children, with particular emphasis on those patients who had experienced life-threatening asthma attacks.


METHODS
Forty-eight children with near-fatal asthma, 134 children with mild-to-moderate asthma, 69 children with allergic disorders but no asthma, and 107 nonasthmatic nonatopic control children were genotyped through use of a PCR-based assay.


RESULTS
No significant difference was demonstrated for frequency of the RANTES -28C/G polymorphism when the mild-to-moderate asthma, atopic/nonasthmatic, and normal control groups were compared. The RANTES -28G allele was present in a significantly higher proportion of the children with near-fatal asthma compared with the nonasthmatic nonatopic controls (odds ratio, 2.93 [1.41-6.06]; P =.006) and the children with mild-to-moderate asthma (odds ratio, 3.52 [1.73-7.16]; P =.001). The frequency of -28G allele carriage correlated with asthma severity. The RANTES -28G allele was also associated with an increased blood eosinophil count and a higher degree of bronchial hyperresponsiveness. The RANTES -403G/A polymorphism did not influence asthma/atopy susceptibility, blood eosinophil count, or bronchial hyperresponsiveness. Interestingly, a higher frequency of -403A allele carriage was observed in the moderate asthma subgroup compared with the mild asthma analog.


CONCLUSIONS
We conclude that the RANTES -28C/G polymorphism exacerbates asthma severity, representing a genetic risk factor for life-threatening asthma attacks in Chinese children. In addition, the linkage disequilibrium between these 2 polymorphisms is a potential confounder that must be considered in the design and interpretation of RANTES gene association studies.
Yao
Tsung-Chieh
TC
Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Children's Hospital, 5 Fu-Hsin Street, Kweishan, Taoyuan, Taiwan, ROC.
Kuo
Ming-Ling
ML
See
Lai-Chu
LC
Chen
Li-Chen
LC
Yan
Dah-Chin
DC
Ou
Liang-Shiou
LS
Shaw
Cheng-Kuang
CK
Huang
Jing-Long
JL
D001249:Asthma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D016535:Bronchial Hyperreactivity / Q000235:genetics; D018946:Chemokine CCL5 / Q000235:genetics*; D002648:Child; D002681:China; D004802:Eosinophilia / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics; D007073:Immunoglobulin E / Q000097:blood; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
D018946:Chemokine CCL5; D007073:Immunoglobulin E