title: Polymorphisms in interleukin 8 and its receptors (IL8, IL8RA and IL8RB) and association of common IL8 receptor variants with peripheral blood eosinophil counts.
abstract: Airway inflammation is a major factor in the pathogenesis of asthma. Interleukin 8 (IL8) is a potent proinflammatory cytokine that interacts with its receptors, IL8RA and IL8RB. We investigated the genetic polymorphisms in IL8, IL8RA, and IL8RB for any association with risk of asthma and peripheral blood eosinophil counts in a Korean population. By carrying out direct sequencing in 24 individuals, we identified 20 sequence variants within exons and their flanking regions, including the 1.5 kb promoter regions of IL8, IL8RA, and IL8RB. Among them, seven common single-nucleotide polymorphisms (SNPs) were selected for genotyping in our asthma cohort (n = 1,439). Two common haplotypes in IL8 and three in IL8RA and IL8RB (defined as one block) were identified. Although none of the polymorphisms showed a significant association with risk of asthma, IL8RA-B ht2 showed a significant association with the peripheral blood eosinophil counts (%) among asthma patients, e.g., lower eosinophil levels among individuals with the homozygous IL8RA-B ht2 (3.55 +/- 3.39%) than among other asthmatic patients (5.52 +/- 5.55%; P (corr) = 0.018). Our findings suggest that polymorphisms and haplotypes in IL8RA and IL8RB might be among the genetic factors underlying production of peripheral blood eosinophil.
authors.affiliation: Department of Genetic Epidemiology, SNP Genetics, Inc., Rm 1407, 14th floor, B-dong, WooLim Lion's Valley, 371-28, Gasan-dong, Geumcheon-Gu, Seoul, 153-803, South Korea.
authors.forename: Hyun Sub
authors.initials: HS
authors.lastname: Cheong
authors.affiliation: Department of Genetic Epidemiology, SNP Genetics, Inc., Rm 1407, 14th floor, B-dong, WooLim Lion's Valley, 371-28, Gasan-dong, Geumcheon-Gu, Seoul, 153-803, South Korea.
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
authors.affiliation: Department of Genetic Epidemiology, SNP Genetics, Inc., Rm 1407, 14th floor, B-dong, WooLim Lion's Valley, 371-28, Gasan-dong, Geumcheon-Gu, Seoul, 153-803, South Korea.
authors.forename: Soo Ok
authors.initials: SO
authors.lastname: Lee
authors.affiliation: Department of Genetic Epidemiology, SNP Genetics, Inc., Rm 1407, 14th floor, B-dong, WooLim Lion's Valley, 371-28, Gasan-dong, Geumcheon-Gu, Seoul, 153-803, South Korea.
authors.forename: Byung Lae
authors.initials: BL
authors.lastname: Park
authors.affiliation: Department of Genetic Epidemiology, SNP Genetics, Inc., Rm 1407, 14th floor, B-dong, WooLim Lion's Valley, 371-28, Gasan-dong, Geumcheon-Gu, Seoul, 153-803, South Korea.
authors.forename: Yoo Hyun
authors.initials: YH
authors.lastname: Choi
authors.affiliation: Asthma Genome Research Group, Soonchunhyang University Hospital, Seoul, South Korea.
authors.forename: Gun Il
authors.initials: GI
authors.lastname: Lim
authors.affiliation: Asthma Genome Research Group, Ajuo University Hospital, Seoul, South Korea.
authors.forename: Soo Taek
authors.initials: ST
authors.lastname: Uh
authors.affiliation: Asthma Genome Research Group, Ulsan University Hospital, Seoul, South Korea.
authors.forename: Young Hun
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Asthma Genome Research Group, Choong-Ang University, Seoul, South Korea.
authors.forename: Jong-Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: National Genome Research Institute, National Institute of Health, 5 Nokbun-dong, Eunpyung-ku, Seoul, 122-701, South Korea.
authors.forename: Jong-Keuk
authors.initials: JK
authors.lastname: Lee
authors.affiliation: National Genome Research Institute, National Institute of Health, 5 Nokbun-dong, Eunpyung-ku, Seoul, 122-701, South Korea.
authors.forename: Hung Tae
authors.initials: HT
authors.lastname: Kim
authors.affiliation: National Genome Research Institute, National Institute of Health, 5 Nokbun-dong, Eunpyung-ku, Seoul, 122-701, South Korea.
authors.forename: Ha-Jung
authors.initials: HJ
authors.lastname: Ryu
authors.affiliation: National Genome Research Institute, National Institute of Health, 5 Nokbun-dong, Eunpyung-ku, Seoul, 122-701, South Korea.
authors.forename: Ka-Kyung
authors.initials: KK
authors.lastname: Kim
authors.affiliation: National Genome Research Institute, National Institute of Health, 5 Nokbun-dong, Eunpyung-ku, Seoul, 122-701, South Korea.
authors.forename: Bok Ghee
authors.initials: BG
authors.lastname: Han
authors.affiliation: National Genome Research Institute, National Institute of Health, 5 Nokbun-dong, Eunpyung-ku, Seoul, 122-701, South Korea.
authors.forename: Jun Woo
authors.initials: JW
authors.lastname: Kim
authors.affiliation: National Genome Research Institute, National Institute of Health, 5 Nokbun-dong, Eunpyung-ku, Seoul, 122-701, South Korea.
authors.forename: Kuchan
authors.initials: K
authors.lastname: Kimm
authors.affiliation: National Genome Research Institute, National Institute of Health, 5 Nokbun-dong, Eunpyung-ku, Seoul, 122-701, South Korea. ohbs@nih.go.kr.
authors.forename: Bermseok
authors.initials: B
authors.lastname: Oh
authors.affiliation: Asthma Genome Research Group, Soonchunhyang University Hospital, Seoul, South Korea. schalr@schbc.ac.kr.|Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, 1174, Jung Dong, Wonmi-Gu, Bucheon, Gyeonggi Do, 420-021, South Korea. schalr@schbc.ac.kr.
authors.forename: Choon-Sik
authors.initials: CS
authors.lastname: Park
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000097:blood / Q000235:genetics / Q000276:immunology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D007723:Korea; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D023062:Receptors, Interleukin-8A / Q000235:genetics*; D023063:Receptors, Interleukin-8B / Q000235:genetics*; D012307:Risk Factors
chemical_list: D016209:Interleukin-8; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B