title: Association of Eotaxin gene family with asthma and serum total IgE.
abstract: 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.
authors.affiliation: Department of Genetic Epidemiology, SNP Genetics Inc., 11th Floor, MaeHun B/D, 13 Chongro 4 Ga, Chongro-Gu, Seoul 110-834, Korea.
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
authors.forename: Lyoung Hyo
authors.initials: LH
authors.lastname: Kim
authors.forename: Byung Lae
authors.initials: BL
authors.lastname: Park
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Jung
authors.forename: Jun Yeon
authors.initials: JY
authors.lastname: Kim
authors.forename: Il-Yup
authors.initials: IY
authors.lastname: Chung
authors.forename: Jung Sun
authors.initials: JS
authors.lastname: Kim
authors.forename: June Hyuk
authors.initials: JH
authors.lastname: Lee
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Chung
authors.forename: Yong Hoon
authors.initials: YH
authors.lastname: Kim
authors.forename: Hae-Sim
authors.initials: HS
authors.lastname: Park
authors.forename: Jeong Hee
authors.initials: JH
authors.lastname: Choi
authors.forename: Young Mok
authors.initials: YM
authors.lastname: Lee
authors.forename: Sung Woo
authors.initials: SW
authors.lastname: Park
authors.forename: Byoung Whui
authors.initials: BW
authors.lastname: Choi
authors.forename: Soo-Jong
authors.initials: SJ
authors.lastname: Hong
authors.forename: Choon-Sik
authors.initials: CS
authors.lastname: Park
mesh_terms: 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
chemical_list: 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