Association of Eotaxin gene family with asthma and serum total IgE.
The Eotaxin gene family (Eotaxin1, Eotaxin2 and Eotaxin3) recruits and activates CCR3-bearing cells such as eosinophils, mast cells and Th2 lymphocytes that play a major role in allergic disorders. To date, the effect of polymorphisms of Eotaxin genes on asthma phenotypes has not been thoroughly examined. In our research, we sequenced whole regions of the Eotaxin gene family to identify polymorphisms, which may be involved in the development of asthma and total serum IgE. We have identified 37 SNPs in the Exotaxin gene family (Exotaxin1, 2 and 3), and 17 common polymorphic sites were selected for genotyping in our asthma cohort (n=721). Statistical analysis revealed that the EOT2+1265A>G G* allele showed significantly lower frequency in asthmatics than in normal healthy controls (0.14 versus 0.23, P=0.002), and that distribution of the EOT2+1265A>G G* allele-containing genotypes was also much lower in asthmatics (26.3 versus 40.8%, P=0.003). In addition, a non-synonymous SNP in Eotaxin1, EOT1+123Ala>Thr showed significant association with total serum IgE levels (P=0.002-0.02). The effect of EOT1+123Ala>Thr on total serum IgE appeared in a gene-dose-dependent manner. Our findings suggest that the development of asthma may be associated with EOT2+1265A>G polymorphisms, and the susceptibility to high IgE production may be attributed to the EOT1+123Ala>Thr polymorphism. Eotaxin variation/haplotype information identified in this study might provide valuable insights into strategies for the control of asthma.
Shin
Hyoung Doo
HD
Department of Genetic Epidemiology, SNP Genetics Inc., 11th Floor, MaeHun B/D, 13 Chongro 4 Ga, Chongro-Gu, Seoul 110-834, Korea.
Kim
Lyoung Hyo
LH
Park
Byung Lae
BL
Jung
Ji Hyun
JH
Kim
Jun Yeon
JY
Chung
Il-Yup
IY
Kim
Jung Sun
JS
Lee
June Hyuk
JH
Chung
Sun Hee
SH
Kim
Yong Hoon
YH
Park
Hae-Sim
HS
Choi
Jeong Hee
JH
Lee
Young Mok
YM
Park
Sung Woo
SW
Choi
Byoung Whui
BW
Hong
Soo-Jong
SJ
Park
Choon-Sik
CS
D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000235:genetics* / Q000276:immunology; D054413:Chemokine CCL11; D054423:Chemokine CCL24; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000235:genetics*; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values
C515456:CCL11 protein, human; C515484:CCL24 protein, human; C120429:CCL26 protein, human; D054413:Chemokine CCL11; D054423:Chemokine CCL24; D000075906:Chemokine CCL26; D019742:Chemokines, CC; D007073:Immunoglobulin E