Tae-Joon Park1, Jong-Sook Park2, Hyun Sub Cheong3, Byung-Lae Park3, Lyoung Hyo Kim3, Jeong Seok Heo2, Yang Ki Kim4, Ki-Up Kim4, Soo-Taek Uh4, Ho Sung Lee5, Joo-Ock Na5, Ki-Hyun Seo5, Jae-Sung Choi5, Yong Hoon Kim5, Myung-Sin Kim6, Choon-Sik Park7, Hyoung Doo Shin8. 1. Department of Life Science, Sogang University, 35, Baekbeom-ro, Mapo-gu, Seoul 121-742, Republic of Korea. 2. Division of Allergy and Respiratory Medicine, Soonchunhyang University Bucheon Hospital, 1174, Jung-dong, Wonmi-gu, Gyeonggi-do 420-020, Republic of Korea. 3. Department of Genetic Epidemiology, SNP Genetics, Inc., 35, Baekbeom-ro, Mapo-gu, Seoul 121-742, Republic of Korea. 4. Division of Allergy and Respiratory Medicine, Soonchunhyang University Seoul Hospital, 59, Daesagwan-ro, Yongsan-gu, Seoul 140-887, Republic of Korea. 5. Division of Allergy and Respiratory Medicine, Soonchunhyang University Cheonan Hospital, 23-20, Byeongmyeong-dong, Dongnam-gu, Cheonan, Chungcheongnam-do 330-721, Republic of Korea. 6. Division of Allergy and Respiratory Medicine, Soonchunhyang University Gumi Hospital, 250, Gongdan-dong, Gumi, Kyungsangbook-do 730-706, Republic of Korea. 7. Division of Allergy and Respiratory Medicine, Soonchunhyang University Bucheon Hospital, 1174, Jung-dong, Wonmi-gu, Gyeonggi-do 420-020, Republic of Korea. Electronic address: schalr@schmc.ac.kr. 8. Department of Life Science, Sogang University, 35, Baekbeom-ro, Mapo-gu, Seoul 121-742, Republic of Korea; Department of Genetic Epidemiology, SNP Genetics, Inc., 35, Baekbeom-ro, Mapo-gu, Seoul 121-742, Republic of Korea. Electronic address: hdshin@sogang.ac.kr.
Abstract
OBJECTIVES: Asthma can be suppressed by inhaled corticosteroids (ICS). However, response to ICS shows marked inter-individual variability. This study is aimed to identify the genetic variants associated with the change in the percentage of forced expiratory volume in 1second (%ΔFEV1) following ICS treatment. METHODS: A genome-wide association study was performed in a Korean asthmatic cohort. To further investigate these genetic associations, 11 additional single-nucleotide polymorphisms (SNPs) on the allantoicase (ALLC) gene were selected from the HapMap database and genotyped in the same asthmatic patients in the follow-up study. RESULTS: In a genome-wide study, we identified the lowest P-value in ALLC, but none of the SNPs met the genome-wide association criteria (P<1.0×10(-8)). However, among 25 SNPs on ALLC in the follow-up study, 6 variants showed significant associations with the mean %ΔFEV1 in the study subjects (P<3.73×10(-6)). CONCLUSIONS: Although the associated signals could not overcome the genome-wide multiple correction due to small sample size (n=189), our results suggest that associated SNPs of ALLC might be genetic predictors of response to ICS, at least with respect to ΔFEV1 in Korean asthmatics.
OBJECTIVES: Asthma can be suppressed by inhaled corticosteroids (ICS). However, response to ICS shows marked inter-individual variability. This study is aimed to identify the genetic variants associated with the change in the percentage of forced expiratory volume in 1second (%ΔFEV1) following ICS treatment. METHODS: A genome-wide association study was performed in a Korean asthmatic cohort. To further investigate these genetic associations, 11 additional single-nucleotide polymorphisms (SNPs) on the allantoicase (ALLC) gene were selected from the HapMap database and genotyped in the same asthmatic patients in the follow-up study. RESULTS: In a genome-wide study, we identified the lowest P-value in ALLC, but none of the SNPs met the genome-wide association criteria (P<1.0×10(-8)). However, among 25 SNPs on ALLC in the follow-up study, 6 variants showed significant associations with the mean %ΔFEV1 in the study subjects (P<3.73×10(-6)). CONCLUSIONS: Although the associated signals could not overcome the genome-wide multiple correction due to small sample size (n=189), our results suggest that associated SNPs of ALLC might be genetic predictors of response to ICS, at least with respect to ΔFEV1 in Korean asthmatics.
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