Association of defensin β-1 gene polymorphisms with asthma

Hara Levy; Benjamin A. Raby; Stephen Lake; Kelan G. Tantisira; David Kwiatkowski; Ross Lazarus; Edwin K. Silverman; Brent Richter; Walter T. Klimecki; Donata Vercelli; Fernando D. Martinez; Scott T. Weiss

doi:10.1016/j.jaci.2004.11.013

Association of defensin β-1 gene polymorphisms with asthma

Hara Levy^*, Benjamin A. Raby, Stephen Lake, Kelan G. Tantisira, David Kwiatkowski, Ross Lazarus, Edwin K. Silverman, Brent Richter, Walter T. Klimecki, Donata Vercelli, Fernando D. Martinez, Scott T. Weiss

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

79 Scopus citations

Abstract

Background: Defensins are antimicrobial peptides that may take part in airway inflammation and hyperresponsiveness. We characterized the genetic diversity in the defensin β-1 (DEFB1) locus and tested for an association between common genetic variants and asthma diagnosis. Methods: To identify single nucleotide polymorphisms (SNPs), we resequenced this gene in 23 self-defined European Americans and 24 African Americans. To test whether DEFB1 genetic variants are associated with asthma, we genotyped 4 haplotype-tag SNPs in 517 asthmatic and 519 control samples from the Nurses' Health Study (NHS) and performed a case-control association analysis. To replicate these findings, we evaluated the DEFB1 polymorphisms in a second cohort from the Childhood Asthma Management Program. Results: Within the NHS, single SNP testing suggested an association between asthma diagnosis and a 5′ genomic SNP (g.-1816 T>C; P = .025) and intronic SNP (IVS+692 G>A; P = .054). A significant association between haplotype (Adenine, Cytosine, Thymine, Adenine [ACTA]) and asthma (P = .024) was also identified. Associations between asthma diagnosis and both DEFB1 polymorphisms were observed in Childhood Asthma Management Program, a second cohort: g.-1816 T>C and IVS+692 G>A demonstrated significant transmission distortion (P = .05 and .007, respectively). Transmission distortion was not observed in male subjects. The rare alleles (-1816C and +692A) were undertransmitted to offspring with asthma, suggesting a protective effect, contrary to the findings in the NHS cohort. Similar effects were evident at the haplotype level: ACTA was undertransmitted (P = .04) and was more prominent in female subjects (P = .007). Conclusion: Variation in DEFB1 contributes to asthma diagnosis, with apparent gender-specific effects.

Original language	English (US)
Pages (from-to)	252-258
Number of pages	7
Journal	Journal of Allergy and Clinical Immunology
Volume	115
Issue number	2
DOIs	https://doi.org/10.1016/j.jaci.2004.11.013
State	Published - Feb 2005

Funding

We acknowledge the assistance of the NHS and its participants, particularly Dr Frank E. Speizer and Dr Carlos A. Camargo, who obtained asthma diagnosis information in this cohort. We thank all of the CAMP families for their enthusiastic participation. We also acknowledge the CAMP investigators and research team, supported by the National Heart, Lung and Blood Institute, for collection of CAMP Genetics Ancillary Study data. We are grateful for the helpful comments of Dr Gerald Pier and Dr Carl R. Crawford. Soma Datta, Carrie Beck, Jody Senter Sylvia, Allison Brown, Michael Hagar, and Maura Regan provided technical expertise and support. CAMP was supported by contracts N01-HR-16044, 16045, 16046, 16047, 16048, 16049, 16050, 16051, and 16052 from the National Heart, Lung and Blood Institute. The CAMP Genetics Ancillary Study was supported by P01 HL67664 (Dr Weiss) from the National Heart, Lung and Blood Institute. In addition, this work was supported by research grants and contracts K23HL074202-01 (Dr Levy) and 1 U01 HL66795 21 (Dr Weiss) from the National Heart, Lung and Blood Institute.

Keywords

Association studies
Asthma
Asthma genetics
Defensin

ASJC Scopus subject areas

Immunology and Allergy
Immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jaci.2004.11.013

Cite this

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title = "Association of defensin β-1 gene polymorphisms with asthma",

abstract = "Background: Defensins are antimicrobial peptides that may take part in airway inflammation and hyperresponsiveness. We characterized the genetic diversity in the defensin β-1 (DEFB1) locus and tested for an association between common genetic variants and asthma diagnosis. Methods: To identify single nucleotide polymorphisms (SNPs), we resequenced this gene in 23 self-defined European Americans and 24 African Americans. To test whether DEFB1 genetic variants are associated with asthma, we genotyped 4 haplotype-tag SNPs in 517 asthmatic and 519 control samples from the Nurses' Health Study (NHS) and performed a case-control association analysis. To replicate these findings, we evaluated the DEFB1 polymorphisms in a second cohort from the Childhood Asthma Management Program. Results: Within the NHS, single SNP testing suggested an association between asthma diagnosis and a 5′ genomic SNP (g.-1816 T>C; P = .025) and intronic SNP (IVS+692 G>A; P = .054). A significant association between haplotype (Adenine, Cytosine, Thymine, Adenine [ACTA]) and asthma (P = .024) was also identified. Associations between asthma diagnosis and both DEFB1 polymorphisms were observed in Childhood Asthma Management Program, a second cohort: g.-1816 T>C and IVS+692 G>A demonstrated significant transmission distortion (P = .05 and .007, respectively). Transmission distortion was not observed in male subjects. The rare alleles (-1816C and +692A) were undertransmitted to offspring with asthma, suggesting a protective effect, contrary to the findings in the NHS cohort. Similar effects were evident at the haplotype level: ACTA was undertransmitted (P = .04) and was more prominent in female subjects (P = .007). Conclusion: Variation in DEFB1 contributes to asthma diagnosis, with apparent gender-specific effects.",

keywords = "Association studies, Asthma, Asthma genetics, Defensin",

author = "Hara Levy and Raby, {Benjamin A.} and Stephen Lake and Tantisira, {Kelan G.} and David Kwiatkowski and Ross Lazarus and Silverman, {Edwin K.} and Brent Richter and Klimecki, {Walter T.} and Donata Vercelli and Martinez, {Fernando D.} and Weiss, {Scott T.}",

note = "Funding Information: We acknowledge the assistance of the NHS and its participants, particularly Dr Frank E. Speizer and Dr Carlos A. Camargo, who obtained asthma diagnosis information in this cohort. We thank all of the CAMP families for their enthusiastic participation. We also acknowledge the CAMP investigators and research team, supported by the National Heart, Lung and Blood Institute, for collection of CAMP Genetics Ancillary Study data. We are grateful for the helpful comments of Dr Gerald Pier and Dr Carl R. Crawford. Soma Datta, Carrie Beck, Jody Senter Sylvia, Allison Brown, Michael Hagar, and Maura Regan provided technical expertise and support. Funding Information: CAMP was supported by contracts N01-HR-16044, 16045, 16046, 16047, 16048, 16049, 16050, 16051, and 16052 from the National Heart, Lung and Blood Institute. The CAMP Genetics Ancillary Study was supported by P01 HL67664 (Dr Weiss) from the National Heart, Lung and Blood Institute. In addition, this work was supported by research grants and contracts K23HL074202-01 (Dr Levy) and 1 U01 HL66795 21 (Dr Weiss) from the National Heart, Lung and Blood Institute. ",

year = "2005",

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doi = "10.1016/j.jaci.2004.11.013",

language = "English (US)",

volume = "115",

pages = "252--258",

journal = "Journal of Allergy and Clinical Immunology",

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publisher = "Elsevier Inc.",

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TY - JOUR

T1 - Association of defensin β-1 gene polymorphisms with asthma

AU - Levy, Hara

AU - Raby, Benjamin A.

AU - Lake, Stephen

AU - Tantisira, Kelan G.

AU - Kwiatkowski, David

AU - Lazarus, Ross

AU - Silverman, Edwin K.

AU - Richter, Brent

AU - Klimecki, Walter T.

AU - Vercelli, Donata

AU - Martinez, Fernando D.

AU - Weiss, Scott T.

N1 - Funding Information: We acknowledge the assistance of the NHS and its participants, particularly Dr Frank E. Speizer and Dr Carlos A. Camargo, who obtained asthma diagnosis information in this cohort. We thank all of the CAMP families for their enthusiastic participation. We also acknowledge the CAMP investigators and research team, supported by the National Heart, Lung and Blood Institute, for collection of CAMP Genetics Ancillary Study data. We are grateful for the helpful comments of Dr Gerald Pier and Dr Carl R. Crawford. Soma Datta, Carrie Beck, Jody Senter Sylvia, Allison Brown, Michael Hagar, and Maura Regan provided technical expertise and support. Funding Information: CAMP was supported by contracts N01-HR-16044, 16045, 16046, 16047, 16048, 16049, 16050, 16051, and 16052 from the National Heart, Lung and Blood Institute. The CAMP Genetics Ancillary Study was supported by P01 HL67664 (Dr Weiss) from the National Heart, Lung and Blood Institute. In addition, this work was supported by research grants and contracts K23HL074202-01 (Dr Levy) and 1 U01 HL66795 21 (Dr Weiss) from the National Heart, Lung and Blood Institute.

PY - 2005/2

Y1 - 2005/2

N2 - Background: Defensins are antimicrobial peptides that may take part in airway inflammation and hyperresponsiveness. We characterized the genetic diversity in the defensin β-1 (DEFB1) locus and tested for an association between common genetic variants and asthma diagnosis. Methods: To identify single nucleotide polymorphisms (SNPs), we resequenced this gene in 23 self-defined European Americans and 24 African Americans. To test whether DEFB1 genetic variants are associated with asthma, we genotyped 4 haplotype-tag SNPs in 517 asthmatic and 519 control samples from the Nurses' Health Study (NHS) and performed a case-control association analysis. To replicate these findings, we evaluated the DEFB1 polymorphisms in a second cohort from the Childhood Asthma Management Program. Results: Within the NHS, single SNP testing suggested an association between asthma diagnosis and a 5′ genomic SNP (g.-1816 T>C; P = .025) and intronic SNP (IVS+692 G>A; P = .054). A significant association between haplotype (Adenine, Cytosine, Thymine, Adenine [ACTA]) and asthma (P = .024) was also identified. Associations between asthma diagnosis and both DEFB1 polymorphisms were observed in Childhood Asthma Management Program, a second cohort: g.-1816 T>C and IVS+692 G>A demonstrated significant transmission distortion (P = .05 and .007, respectively). Transmission distortion was not observed in male subjects. The rare alleles (-1816C and +692A) were undertransmitted to offspring with asthma, suggesting a protective effect, contrary to the findings in the NHS cohort. Similar effects were evident at the haplotype level: ACTA was undertransmitted (P = .04) and was more prominent in female subjects (P = .007). Conclusion: Variation in DEFB1 contributes to asthma diagnosis, with apparent gender-specific effects.

AB - Background: Defensins are antimicrobial peptides that may take part in airway inflammation and hyperresponsiveness. We characterized the genetic diversity in the defensin β-1 (DEFB1) locus and tested for an association between common genetic variants and asthma diagnosis. Methods: To identify single nucleotide polymorphisms (SNPs), we resequenced this gene in 23 self-defined European Americans and 24 African Americans. To test whether DEFB1 genetic variants are associated with asthma, we genotyped 4 haplotype-tag SNPs in 517 asthmatic and 519 control samples from the Nurses' Health Study (NHS) and performed a case-control association analysis. To replicate these findings, we evaluated the DEFB1 polymorphisms in a second cohort from the Childhood Asthma Management Program. Results: Within the NHS, single SNP testing suggested an association between asthma diagnosis and a 5′ genomic SNP (g.-1816 T>C; P = .025) and intronic SNP (IVS+692 G>A; P = .054). A significant association between haplotype (Adenine, Cytosine, Thymine, Adenine [ACTA]) and asthma (P = .024) was also identified. Associations between asthma diagnosis and both DEFB1 polymorphisms were observed in Childhood Asthma Management Program, a second cohort: g.-1816 T>C and IVS+692 G>A demonstrated significant transmission distortion (P = .05 and .007, respectively). Transmission distortion was not observed in male subjects. The rare alleles (-1816C and +692A) were undertransmitted to offspring with asthma, suggesting a protective effect, contrary to the findings in the NHS cohort. Similar effects were evident at the haplotype level: ACTA was undertransmitted (P = .04) and was more prominent in female subjects (P = .007). Conclusion: Variation in DEFB1 contributes to asthma diagnosis, with apparent gender-specific effects.

KW - Association studies

KW - Asthma

KW - Asthma genetics

KW - Defensin

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SN - 0091-6749

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SP - 252

EP - 258

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 2

ER -

Association of defensin β-1 gene polymorphisms with asthma

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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