Association between genetic variations of vascular endothelial growth factor receptor 2 and atopy in the Korean population.
BACKGROUND
Vascular endothelial growth factor (VEGF) has been suggested to be a key mediator in the development of atopy and T(H)2 inflammation.


OBJECTIVE
We sought to evaluate the effects of variations in the gene coding VEGF receptor (VEGFR) 2 on intermediate phenotypes of asthma in the Korean population.


METHODS
A cohort of 2055 children and adolescents responded to a questionnaire concerning asthma symptoms and risk factors and underwent methacholine bronchial challenge and skin tests. The VEGFR2 gene, including the promoter area, was sequenced on 24 healthy subjects to discover informative single nucleotide polymorphisms (SNPs; minor allele frequency >2%). After haplotype reconstruction, 4 tagging SNPs (IVS6+54A>G, +889G>A, +1416T>A, and IVS25-92G>A) were scored. These SNPs were also scored in 480 adult asthmatic patients to verify the above genetic association study.


RESULTS
The prevalence of atopy was associated with a single SNP (+889G>A) of VEGFR2 with borderline significance (P = .048; relative risk, 1.13; 95% CI, 1.00-1.28). However, haplotype analysis showed that the atopy prevalence was strongly associated with a haplotype (AGAG) of VEGFR2 (P = .002; relative risk, 1.25; 95% CI, 1.09-1.42). As for airway hyperresponsiveness, neither individual SNPs nor haplotypes were found to be associated. Interestingly, the significant association was also found between atopy and the AGAG haplotype among adult asthmatic patients (P = .008; odds ratio, 1.66; 95% CI, 1.14-2.44).


CONCLUSIONS
The present study demonstrated that genetic variations of VEGFR2 are significantly associated with atopy in the Korean population.
Park
Heung-Woo
HW
Department of Internal Medicine, Seoul National University College of Medicine, Yongun-dong, Chongno-gu, Korea.
Lee
Jong-Eun
JE
Shin
Eun-Soon
ES
Lee
Jae-Young
JY
Bahn
Joon-Woo
JW
Oh
Heung-Bum
HB
Oh
Sun-Young
SY
Cho
Sang-Heon
SH
Moon
Hee-Bum
HB
Min
Kyung-Up
KU
Elias
Jack A
JA
Kim
You-Young
YY
Kim
Yoon-Keun
YK
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000453:epidemiology / Q000235:genetics; D002648:Child; D015331:Cohort Studies; D005260:Female; D005799:Genes, Dominant; D005808:Genes, Recessive; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000453:epidemiology / Q000235:genetics*; D007723:Korea / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*
D040301:Vascular Endothelial Growth Factor Receptor-2