Volume 16, Issue 4 pp. 630-638

Association of 5-hydroxytryptamine (serotonin) receptor 4 (5-HTR4) gene polymorphisms with asthma

TAE-HOON KIM

TAE-HOON KIM

Genome Research Center for Allergy and Respiratory Disease, Soonchunhyang University Bucheon Hospital, Bucheon

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SUNG-HYE AN

SUNG-HYE AN

Genome Research Center for Allergy and Respiratory Disease, Soonchunhyang University Bucheon Hospital, Bucheon

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JI-YEON CHA

JI-YEON CHA

Genome Research Center for Allergy and Respiratory Disease, Soonchunhyang University Bucheon Hospital, Bucheon

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EUN-KYONG SHIN

EUN-KYONG SHIN

Genome Research Center for Allergy and Respiratory Disease, Soonchunhyang University Bucheon Hospital, Bucheon

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JI-YEON LEE

JI-YEON LEE

Genome Research Center for Allergy and Respiratory Disease, Soonchunhyang University Bucheon Hospital, Bucheon

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SANG-HYUK YOON

SANG-HYUK YOON

Genome Research Center for Allergy and Respiratory Disease, Soonchunhyang University Bucheon Hospital, Bucheon

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YOUNG-MOK LEE

YOUNG-MOK LEE

Division of Allergy and Respiratory Medicine, Soonchunhyang University Hospital

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SOO-TAEK UH

SOO-TAEK UH

Division of Allergy and Respiratory Medicine, Soonchunhyang University Hospital

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SUNG-WOO PARK

SUNG-WOO PARK

Genome Research Center for Allergy and Respiratory Disease, Soonchunhyang University Bucheon Hospital, Bucheon

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JONG-SOOK PARK

JONG-SOOK PARK

Genome Research Center for Allergy and Respiratory Disease, Soonchunhyang University Bucheon Hospital, Bucheon

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YOUNG-HOON KIM

YOUNG-HOON KIM

Division of Allergy and Respiratory Medicine, Soonchunhyang University Hospital, Gumi-si

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JAE-SUNG CHOI

JAE-SUNG CHOI

Division of Allergy and Respiratory Medicine, Soonchunhyang University Hospital, Cheonan, Korea

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SOO-OK LEE

SOO-OK LEE

Department of Life Science, Sogang University, Seoul

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BYUNG-LAE PARK

BYUNG-LAE PARK

Department of Genetic Epidemiology, SNP Genetics, Inc.

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HYUNG-DOO SHIN

HYUNG-DOO SHIN

Department of Genetic Epidemiology, SNP Genetics, Inc.

Department of Life Science, Sogang University, Seoul

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CHOON-SIK PARK

Corresponding Author

CHOON-SIK PARK

Genome Research Center for Allergy and Respiratory Disease, Soonchunhyang University Bucheon Hospital, Bucheon

Choon-Sik Park, Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, 1174, Jung-Dong, Wonmi-Ku, Bucheon, Kyeonggi-Do 420-020, Korea. Email: [email protected]Search for more papers by this author
First published: 08 March 2011
Citations: 10

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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