Polymorphisms in interleukin 8 and its receptors (IL8, IL8RA and IL8RB) and association of common IL8 receptor variants with peripheral blood eosinophil counts.
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.
Cheong
Hyun Sub
HS
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.
Shin
Hyoung Doo
HD
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.
Lee
Soo Ok
SO
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.
Park
Byung Lae
BL
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.
Choi
Yoo Hyun
YH
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.
Lim
Gun Il
GI
Asthma Genome Research Group, Soonchunhyang University Hospital, Seoul, South Korea.
Uh
Soo Taek
ST
Asthma Genome Research Group, Ajuo University Hospital, Seoul, South Korea.
Kim
Young Hun
YH
Asthma Genome Research Group, Ulsan University Hospital, Seoul, South Korea.
Lee
Jong-Young
JY
Asthma Genome Research Group, Choong-Ang University, Seoul, South Korea.
Lee
Jong-Keuk
JK
National Genome Research Institute, National Institute of Health, 5 Nokbun-dong, Eunpyung-ku, Seoul, 122-701, South Korea.
Kim
Hung Tae
HT
National Genome Research Institute, National Institute of Health, 5 Nokbun-dong, Eunpyung-ku, Seoul, 122-701, South Korea.
Ryu
Ha-Jung
HJ
National Genome Research Institute, National Institute of Health, 5 Nokbun-dong, Eunpyung-ku, Seoul, 122-701, South Korea.
Kim
Ka-Kyung
KK
National Genome Research Institute, National Institute of Health, 5 Nokbun-dong, Eunpyung-ku, Seoul, 122-701, South Korea.
Han
Bok Ghee
BG
National Genome Research Institute, National Institute of Health, 5 Nokbun-dong, Eunpyung-ku, Seoul, 122-701, South Korea.
Kim
Jun Woo
JW
National Genome Research Institute, National Institute of Health, 5 Nokbun-dong, Eunpyung-ku, Seoul, 122-701, South Korea.
Kimm
Kuchan
K
National Genome Research Institute, National Institute of Health, 5 Nokbun-dong, Eunpyung-ku, Seoul, 122-701, South Korea.
Oh
Bermseok
B
National Genome Research Institute, National Institute of Health, 5 Nokbun-dong, Eunpyung-ku, Seoul, 122-701, South Korea. ohbs@nih.go.kr.
Park
Choon-Sik
CS
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.
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
D016209:Interleukin-8; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B