Association of 5-hydroxytryptamine (serotonin) receptor 4 (5-HTR4) gene polymorphisms with asthma
- Authors
- Kim, Tae-Hoon; An, Sung-Hye; Cha, Ji-Yeon; Shin, Eun-Kyong; Lee, Ji-Yeon; Yoon, Sang-Hyuk; Lee, Young-Mok; Uh, Soo-Taek; Park, Sung-Woo; Park, Jong-Sook; Kim, Young-Hoon; Choi, Jae-Sung; Lee, Soo-Ok; Park, Byung-Lae; Shin, Hyung-Doo; Park, Choon-Sik
- Issue Date
- May-2011
- Publisher
- Blackwell Publishing Inc.
- Keywords
- 5-hydroxytryptamine receptor 4; asthma; haploidy; logistic regression; single nucleotide polymorphism
- Citation
- Respirology, v.16, no.4, pp 630 - 638
- Pages
- 9
- Journal Title
- Respirology
- Volume
- 16
- Number
- 4
- Start Page
- 630
- End Page
- 638
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/16570
- DOI
- 10.1111/j.1440-1843.2011.01963.x
- ISSN
- 1323-7799
1440-1843
- Abstract
- Background and objective: The neurotransmitter, 5-hydroxytryptamine, acts as an immunomodulator by stimulating the release of inflammatory cytokines and regulating the function of dendritic cells and monocytes. The 5-hydroxytryptamine receptor 4 (HTR4) gene is located in a region previously linked to an increased risk of asthma and atopy. The aim of this study was to investigate the association between HTR4 and asthma. Methods: Thirty-two single nucleotide polymorphisms (SNP) in HTR4 were investigated by direct sequencing of 24 DNA samples from unrelated Korean subjects. Results: The 32 genetic variants comprised 22 intronic SNP, two SNP in the 3'-untranslated region (exon 7) and eight SNP in the 3'-downstream region. Logistic regression analysis showed that two intronic polymorphisms were significantly associated with the risk of asthma. Two minor HTR4 alleles, +142828G > A and + 122769G > A, occurred at significantly higher frequencies in the asthmatic group than in the healthy control group (49.59% vs 42.29%, P = 0.003, and 47.99% vs 40.35%, P = 0.008, respectively), and these differences remained significant after correction for multiple testing (P = 0.05, dominant mode of inheritance; and P = 0.03, dominant mode, respectively). Haplotype analysis revealed three haplotype blocks. The frequency of haplotype 1 in block 2 was significantly higher in asthmatics (P = 0.003, dominant mode), whereas the frequency of haplotype 4 in block 3 was significantly lower in asthmatics (P = 0.0009, dominant mode). Conclusions: SNP and haplotypes of the HTR4 gene were associated with the asthma phenotype and genetic variation of HTR4 may affect susceptibility to the development of asthma.
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Collections - College of Medicine > Department of Internal Medicine > 1. Journal Articles
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