Genome-wide interaction study of dust mite allergen on lung function in children with asthma
Background Childhood asthma is likely the result of gene-by-environment (G × E) interactions. Dust mite is a known risk factor for asthma morbidity. Yet, there have been no genome-wide G × E studies of dust mite allergen on asthma-related phenotypes. Objective We sought to identify genetic variants...
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| creator | Forno, Erick, MD, MPH Sordillo, Joanne, MD, MPH Brehm, John, MD, MPH Chen, Wei, PhD Benos, Takis, PhD Yan, Qi, PhD Avila, Lydiana, MD Soto-Quirós, Manuel, MD Cloutier, Michelle M., MD Colón-Semidey, Angel, MD Alvarez, Maria, MD Acosta-Pérez, Edna, PhD Weiss, Scott T., MD, MS Litonjua, Augusto A., MD, MPH Canino, Glorisa, PhD Celedón, Juan C., MD, DrPH, FAAAAI |
| description | Background Childhood asthma is likely the result of gene-by-environment (G × E) interactions. Dust mite is a known risk factor for asthma morbidity. Yet, there have been no genome-wide G × E studies of dust mite allergen on asthma-related phenotypes. Objective We sought to identify genetic variants whose effects on lung function in children with asthma are modified by the level of dust mite allergen exposure. Methods A genome-wide interaction analysis of dust mite allergen level and lung function was performed in a cohort of Puerto Rican children with asthma (Puerto Rico Genetics of Asthma and Lifestyle [PRGOAL]). Replication was attempted in 2 independent cohorts, the Childhood Asthma Management Program (CAMP) and the Genetics of Asthma in Costa Rica Study. Results Single nucleotide polymorphism (SNP) rs117902240 showed a significant interaction effect on FEV1 with dust mite allergen level in PRGOAL (interaction P = 3.1 × 10−8 ), and replicated in the same direction in CAMP white children and CAMP Hispanic children (combined interaction P = .0065 for replication cohorts and 7.4 × 10−9 for all cohorts). Rs117902240 was positively associated with FEV1 in children exposed to low dust mite allergen levels, but negatively associated with FEV1 in children exposed to high levels. This SNP is on chromosome 8q24, adjacent to a binding site for CCAAT/enhancer-binding protein beta, a transcription factor that forms part of the IL-17 signaling pathway. None of the SNPs identified for FEV1 /forced vital capacity replicated in the independent cohorts. Conclusions Dust mite allergen exposure modifies the estimated effect of rs117902240 on FEV1 in children with asthma. Analysis of existing data suggests that this SNP may have transcription factor regulatory functions. |
| doi_str_mv | 10.1016/j.jaci.2016.12.967 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5544591</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0091674917301549</els_id><sourcerecordid>1865821972</sourcerecordid><originalsourceid>FETCH-LOGICAL-c538t-ff2c2ae79d61db6d20bde23a8734d206da6655db4b245e1d866221493ffcbf813</originalsourceid><addsrcrecordid>eNp9kkFrFTEQxxdR7LP6BTxIwIuXXZPsJpuAFErRKhQ8qDchZJPZ9_LMZmuSbXnf3iyvVu3BUzLMb_7MzH-q6iXBDcGEv903e21cQ8u_IbSRvH9UbQiWfc0FZY-rDcaS1Lzv5En1LKU9LnEr5NPqhArCeyzZpvp-CWGeoL51FpALGaI22c0BpbzYA5pHZJeU0eQyIO09xC0EVNJ-CVs0LuEIu4DMznkbS_LW5R3SKe8m_bx6Mmqf4MXde1p9-_D-68XH-urz5aeL86vasFbkehypoRp6aTmxA7cUDxZoq0XfdiXgVnPOmB26gXYMiBWcU0o62Y6jGUZB2tPq7Kh7vQwTWAMhR-3VdXSTjgc1a6f-zQS3U9v5RjHWdUyuAm_uBOL8c4GU1eSSAe91gHlJigjOBCWypwV9_QDdz0sMZTxFZCc5a6mQhaJHysQ5pQjjfTMEq9U8tVereWo1TxGqinml6NXfY9yX_HarAO-OAJRl3jiIKhkHwYB1EUxWdnb_1z97UG68C85o_wMOkP7MoRJVWH1Zz2e9HtK3mLCy7184LcGF</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1949653289</pqid></control><display><type>article</type><title>Genome-wide interaction study of dust mite allergen on lung function in children with asthma</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Forno, Erick, MD, MPH ; Sordillo, Joanne, MD, MPH ; Brehm, John, MD, MPH ; Chen, Wei, PhD ; Benos, Takis, PhD ; Yan, Qi, PhD ; Avila, Lydiana, MD ; Soto-Quirós, Manuel, MD ; Cloutier, Michelle M., MD ; Colón-Semidey, Angel, MD ; Alvarez, Maria, MD ; Acosta-Pérez, Edna, PhD ; Weiss, Scott T., MD, MS ; Litonjua, Augusto A., MD, MPH ; Canino, Glorisa, PhD ; Celedón, Juan C., MD, DrPH, FAAAAI</creator><creatorcontrib>Forno, Erick, MD, MPH ; Sordillo, Joanne, MD, MPH ; Brehm, John, MD, MPH ; Chen, Wei, PhD ; Benos, Takis, PhD ; Yan, Qi, PhD ; Avila, Lydiana, MD ; Soto-Quirós, Manuel, MD ; Cloutier, Michelle M., MD ; Colón-Semidey, Angel, MD ; Alvarez, Maria, MD ; Acosta-Pérez, Edna, PhD ; Weiss, Scott T., MD, MS ; Litonjua, Augusto A., MD, MPH ; Canino, Glorisa, PhD ; Celedón, Juan C., MD, DrPH, FAAAAI</creatorcontrib><description>Background Childhood asthma is likely the result of gene-by-environment (G × E) interactions. Dust mite is a known risk factor for asthma morbidity. Yet, there have been no genome-wide G × E studies of dust mite allergen on asthma-related phenotypes. Objective We sought to identify genetic variants whose effects on lung function in children with asthma are modified by the level of dust mite allergen exposure. Methods A genome-wide interaction analysis of dust mite allergen level and lung function was performed in a cohort of Puerto Rican children with asthma (Puerto Rico Genetics of Asthma and Lifestyle [PRGOAL]). Replication was attempted in 2 independent cohorts, the Childhood Asthma Management Program (CAMP) and the Genetics of Asthma in Costa Rica Study. Results Single nucleotide polymorphism (SNP) rs117902240 showed a significant interaction effect on FEV1 with dust mite allergen level in PRGOAL (interaction P = 3.1 × 10−8 ), and replicated in the same direction in CAMP white children and CAMP Hispanic children (combined interaction P = .0065 for replication cohorts and 7.4 × 10−9 for all cohorts). Rs117902240 was positively associated with FEV1 in children exposed to low dust mite allergen levels, but negatively associated with FEV1 in children exposed to high levels. This SNP is on chromosome 8q24, adjacent to a binding site for CCAAT/enhancer-binding protein beta, a transcription factor that forms part of the IL-17 signaling pathway. None of the SNPs identified for FEV1 /forced vital capacity replicated in the independent cohorts. Conclusions Dust mite allergen exposure modifies the estimated effect of rs117902240 on FEV1 in children with asthma. Analysis of existing data suggests that this SNP may have transcription factor regulatory functions.</description><identifier>ISSN: 0091-6749</identifier><identifier>EISSN: 1097-6825</identifier><identifier>DOI: 10.1016/j.jaci.2016.12.967</identifier><identifier>PMID: 28167095</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adolescent ; Allergens ; Allergies ; Allergy and Immunology ; Antigens, Dermatophagoides - immunology ; Asthma ; Asthma - immunology ; Case-Control Studies ; CCAAT-Enhancer-Binding Proteins - metabolism ; CCAAT/enhancer-binding protein ; CEBPβ ; Child ; Childhood asthma ; Children ; Children & youth ; Chromosome 8 ; Cohort Studies ; Cytokines ; Data processing ; Dust ; dust mite allergen ; Exposure ; Female ; Gene polymorphism ; gene-by-environment interactions ; Gene-Environment Interaction ; Genes ; Genetics ; Genome-Wide Association Study ; genome-wide interaction study ; Genomes ; Households ; Humans ; Interleukin 17 ; Interleukin-17 - metabolism ; Lung - physiology ; lung function ; Lungs ; Male ; Mites ; Morbidity ; Parents & parenting ; Polymorphism, Single Nucleotide ; Protein Binding ; Puerto Rico ; Replication ; Respiratory function ; Respiratory Function Tests ; Risk factors ; Signal transduction ; Single-nucleotide polymorphism ; Studies</subject><ispartof>Journal of allergy and clinical immunology, 2017-10, Vol.140 (4), p.996-1003.e7</ispartof><rights>American Academy of Allergy, Asthma & Immunology</rights><rights>2017 American Academy of Allergy, Asthma & Immunology</rights><rights>Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.</rights><rights>Copyright Elsevier Science Ltd. Oct 1, 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c538t-ff2c2ae79d61db6d20bde23a8734d206da6655db4b245e1d866221493ffcbf813</citedby><cites>FETCH-LOGICAL-c538t-ff2c2ae79d61db6d20bde23a8734d206da6655db4b245e1d866221493ffcbf813</cites><orcidid>0000-0002-9579-1591 ; 0000-0001-6497-9885</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0091674917301549$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28167095$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Forno, Erick, MD, MPH</creatorcontrib><creatorcontrib>Sordillo, Joanne, MD, MPH</creatorcontrib><creatorcontrib>Brehm, John, MD, MPH</creatorcontrib><creatorcontrib>Chen, Wei, PhD</creatorcontrib><creatorcontrib>Benos, Takis, PhD</creatorcontrib><creatorcontrib>Yan, Qi, PhD</creatorcontrib><creatorcontrib>Avila, Lydiana, MD</creatorcontrib><creatorcontrib>Soto-Quirós, Manuel, MD</creatorcontrib><creatorcontrib>Cloutier, Michelle M., MD</creatorcontrib><creatorcontrib>Colón-Semidey, Angel, MD</creatorcontrib><creatorcontrib>Alvarez, Maria, MD</creatorcontrib><creatorcontrib>Acosta-Pérez, Edna, PhD</creatorcontrib><creatorcontrib>Weiss, Scott T., MD, MS</creatorcontrib><creatorcontrib>Litonjua, Augusto A., MD, MPH</creatorcontrib><creatorcontrib>Canino, Glorisa, PhD</creatorcontrib><creatorcontrib>Celedón, Juan C., MD, DrPH, FAAAAI</creatorcontrib><title>Genome-wide interaction study of dust mite allergen on lung function in children with asthma</title><title>Journal of allergy and clinical immunology</title><addtitle>J Allergy Clin Immunol</addtitle><description>Background Childhood asthma is likely the result of gene-by-environment (G × E) interactions. Dust mite is a known risk factor for asthma morbidity. Yet, there have been no genome-wide G × E studies of dust mite allergen on asthma-related phenotypes. Objective We sought to identify genetic variants whose effects on lung function in children with asthma are modified by the level of dust mite allergen exposure. Methods A genome-wide interaction analysis of dust mite allergen level and lung function was performed in a cohort of Puerto Rican children with asthma (Puerto Rico Genetics of Asthma and Lifestyle [PRGOAL]). Replication was attempted in 2 independent cohorts, the Childhood Asthma Management Program (CAMP) and the Genetics of Asthma in Costa Rica Study. Results Single nucleotide polymorphism (SNP) rs117902240 showed a significant interaction effect on FEV1 with dust mite allergen level in PRGOAL (interaction P = 3.1 × 10−8 ), and replicated in the same direction in CAMP white children and CAMP Hispanic children (combined interaction P = .0065 for replication cohorts and 7.4 × 10−9 for all cohorts). Rs117902240 was positively associated with FEV1 in children exposed to low dust mite allergen levels, but negatively associated with FEV1 in children exposed to high levels. This SNP is on chromosome 8q24, adjacent to a binding site for CCAAT/enhancer-binding protein beta, a transcription factor that forms part of the IL-17 signaling pathway. None of the SNPs identified for FEV1 /forced vital capacity replicated in the independent cohorts. Conclusions Dust mite allergen exposure modifies the estimated effect of rs117902240 on FEV1 in children with asthma. Analysis of existing data suggests that this SNP may have transcription factor regulatory functions.</description><subject>Adolescent</subject><subject>Allergens</subject><subject>Allergies</subject><subject>Allergy and Immunology</subject><subject>Antigens, Dermatophagoides - immunology</subject><subject>Asthma</subject><subject>Asthma - immunology</subject><subject>Case-Control Studies</subject><subject>CCAAT-Enhancer-Binding Proteins - metabolism</subject><subject>CCAAT/enhancer-binding protein</subject><subject>CEBPβ</subject><subject>Child</subject><subject>Childhood asthma</subject><subject>Children</subject><subject>Children & youth</subject><subject>Chromosome 8</subject><subject>Cohort Studies</subject><subject>Cytokines</subject><subject>Data processing</subject><subject>Dust</subject><subject>dust mite allergen</subject><subject>Exposure</subject><subject>Female</subject><subject>Gene polymorphism</subject><subject>gene-by-environment interactions</subject><subject>Gene-Environment Interaction</subject><subject>Genes</subject><subject>Genetics</subject><subject>Genome-Wide Association Study</subject><subject>genome-wide interaction study</subject><subject>Genomes</subject><subject>Households</subject><subject>Humans</subject><subject>Interleukin 17</subject><subject>Interleukin-17 - metabolism</subject><subject>Lung - physiology</subject><subject>lung function</subject><subject>Lungs</subject><subject>Male</subject><subject>Mites</subject><subject>Morbidity</subject><subject>Parents & parenting</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Protein Binding</subject><subject>Puerto Rico</subject><subject>Replication</subject><subject>Respiratory function</subject><subject>Respiratory Function Tests</subject><subject>Risk factors</subject><subject>Signal transduction</subject><subject>Single-nucleotide polymorphism</subject><subject>Studies</subject><issn>0091-6749</issn><issn>1097-6825</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kkFrFTEQxxdR7LP6BTxIwIuXXZPsJpuAFErRKhQ8qDchZJPZ9_LMZmuSbXnf3iyvVu3BUzLMb_7MzH-q6iXBDcGEv903e21cQ8u_IbSRvH9UbQiWfc0FZY-rDcaS1Lzv5En1LKU9LnEr5NPqhArCeyzZpvp-CWGeoL51FpALGaI22c0BpbzYA5pHZJeU0eQyIO09xC0EVNJ-CVs0LuEIu4DMznkbS_LW5R3SKe8m_bx6Mmqf4MXde1p9-_D-68XH-urz5aeL86vasFbkehypoRp6aTmxA7cUDxZoq0XfdiXgVnPOmB26gXYMiBWcU0o62Y6jGUZB2tPq7Kh7vQwTWAMhR-3VdXSTjgc1a6f-zQS3U9v5RjHWdUyuAm_uBOL8c4GU1eSSAe91gHlJigjOBCWypwV9_QDdz0sMZTxFZCc5a6mQhaJHysQ5pQjjfTMEq9U8tVereWo1TxGqinml6NXfY9yX_HarAO-OAJRl3jiIKhkHwYB1EUxWdnb_1z97UG68C85o_wMOkP7MoRJVWH1Zz2e9HtK3mLCy7184LcGF</recordid><startdate>20171001</startdate><enddate>20171001</enddate><creator>Forno, Erick, MD, MPH</creator><creator>Sordillo, Joanne, MD, MPH</creator><creator>Brehm, John, MD, MPH</creator><creator>Chen, Wei, PhD</creator><creator>Benos, Takis, PhD</creator><creator>Yan, Qi, PhD</creator><creator>Avila, Lydiana, MD</creator><creator>Soto-Quirós, Manuel, MD</creator><creator>Cloutier, Michelle M., MD</creator><creator>Colón-Semidey, Angel, MD</creator><creator>Alvarez, Maria, MD</creator><creator>Acosta-Pérez, Edna, PhD</creator><creator>Weiss, Scott T., MD, MS</creator><creator>Litonjua, Augusto A., MD, MPH</creator><creator>Canino, Glorisa, PhD</creator><creator>Celedón, Juan C., MD, DrPH, FAAAAI</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SS</scope><scope>7T5</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-9579-1591</orcidid><orcidid>https://orcid.org/0000-0001-6497-9885</orcidid></search><sort><creationdate>20171001</creationdate><title>Genome-wide interaction study of dust mite allergen on lung function in children with asthma</title><author>Forno, Erick, MD, MPH ; Sordillo, Joanne, MD, MPH ; Brehm, John, MD, MPH ; Chen, Wei, PhD ; Benos, Takis, PhD ; Yan, Qi, PhD ; Avila, Lydiana, MD ; Soto-Quirós, Manuel, MD ; Cloutier, Michelle M., MD ; Colón-Semidey, Angel, MD ; Alvarez, Maria, MD ; Acosta-Pérez, Edna, PhD ; Weiss, Scott T., MD, MS ; Litonjua, Augusto A., MD, MPH ; Canino, Glorisa, PhD ; Celedón, Juan C., MD, DrPH, FAAAAI</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c538t-ff2c2ae79d61db6d20bde23a8734d206da6655db4b245e1d866221493ffcbf813</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adolescent</topic><topic>Allergens</topic><topic>Allergies</topic><topic>Allergy and Immunology</topic><topic>Antigens, Dermatophagoides - immunology</topic><topic>Asthma</topic><topic>Asthma - immunology</topic><topic>Case-Control Studies</topic><topic>CCAAT-Enhancer-Binding Proteins - metabolism</topic><topic>CCAAT/enhancer-binding protein</topic><topic>CEBPβ</topic><topic>Child</topic><topic>Childhood asthma</topic><topic>Children</topic><topic>Children & youth</topic><topic>Chromosome 8</topic><topic>Cohort Studies</topic><topic>Cytokines</topic><topic>Data processing</topic><topic>Dust</topic><topic>dust mite allergen</topic><topic>Exposure</topic><topic>Female</topic><topic>Gene polymorphism</topic><topic>gene-by-environment interactions</topic><topic>Gene-Environment Interaction</topic><topic>Genes</topic><topic>Genetics</topic><topic>Genome-Wide Association Study</topic><topic>genome-wide interaction study</topic><topic>Genomes</topic><topic>Households</topic><topic>Humans</topic><topic>Interleukin 17</topic><topic>Interleukin-17 - metabolism</topic><topic>Lung - physiology</topic><topic>lung function</topic><topic>Lungs</topic><topic>Male</topic><topic>Mites</topic><topic>Morbidity</topic><topic>Parents & parenting</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Protein Binding</topic><topic>Puerto Rico</topic><topic>Replication</topic><topic>Respiratory function</topic><topic>Respiratory Function Tests</topic><topic>Risk factors</topic><topic>Signal transduction</topic><topic>Single-nucleotide polymorphism</topic><topic>Studies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Forno, Erick, MD, MPH</creatorcontrib><creatorcontrib>Sordillo, Joanne, MD, MPH</creatorcontrib><creatorcontrib>Brehm, John, MD, MPH</creatorcontrib><creatorcontrib>Chen, Wei, PhD</creatorcontrib><creatorcontrib>Benos, Takis, PhD</creatorcontrib><creatorcontrib>Yan, Qi, PhD</creatorcontrib><creatorcontrib>Avila, Lydiana, MD</creatorcontrib><creatorcontrib>Soto-Quirós, Manuel, MD</creatorcontrib><creatorcontrib>Cloutier, Michelle M., MD</creatorcontrib><creatorcontrib>Colón-Semidey, Angel, MD</creatorcontrib><creatorcontrib>Alvarez, Maria, MD</creatorcontrib><creatorcontrib>Acosta-Pérez, Edna, PhD</creatorcontrib><creatorcontrib>Weiss, Scott T., MD, MS</creatorcontrib><creatorcontrib>Litonjua, Augusto A., MD, MPH</creatorcontrib><creatorcontrib>Canino, Glorisa, PhD</creatorcontrib><creatorcontrib>Celedón, Juan C., MD, DrPH, FAAAAI</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of allergy and clinical immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Forno, Erick, MD, MPH</au><au>Sordillo, Joanne, MD, MPH</au><au>Brehm, John, MD, MPH</au><au>Chen, Wei, PhD</au><au>Benos, Takis, PhD</au><au>Yan, Qi, PhD</au><au>Avila, Lydiana, MD</au><au>Soto-Quirós, Manuel, MD</au><au>Cloutier, Michelle M., MD</au><au>Colón-Semidey, Angel, MD</au><au>Alvarez, Maria, MD</au><au>Acosta-Pérez, Edna, PhD</au><au>Weiss, Scott T., MD, MS</au><au>Litonjua, Augusto A., MD, MPH</au><au>Canino, Glorisa, PhD</au><au>Celedón, Juan C., MD, DrPH, FAAAAI</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genome-wide interaction study of dust mite allergen on lung function in children with asthma</atitle><jtitle>Journal of allergy and clinical immunology</jtitle><addtitle>J Allergy Clin Immunol</addtitle><date>2017-10-01</date><risdate>2017</risdate><volume>140</volume><issue>4</issue><spage>996</spage><epage>1003.e7</epage><pages>996-1003.e7</pages><issn>0091-6749</issn><eissn>1097-6825</eissn><abstract>Background Childhood asthma is likely the result of gene-by-environment (G × E) interactions. Dust mite is a known risk factor for asthma morbidity. Yet, there have been no genome-wide G × E studies of dust mite allergen on asthma-related phenotypes. Objective We sought to identify genetic variants whose effects on lung function in children with asthma are modified by the level of dust mite allergen exposure. Methods A genome-wide interaction analysis of dust mite allergen level and lung function was performed in a cohort of Puerto Rican children with asthma (Puerto Rico Genetics of Asthma and Lifestyle [PRGOAL]). Replication was attempted in 2 independent cohorts, the Childhood Asthma Management Program (CAMP) and the Genetics of Asthma in Costa Rica Study. Results Single nucleotide polymorphism (SNP) rs117902240 showed a significant interaction effect on FEV1 with dust mite allergen level in PRGOAL (interaction P = 3.1 × 10−8 ), and replicated in the same direction in CAMP white children and CAMP Hispanic children (combined interaction P = .0065 for replication cohorts and 7.4 × 10−9 for all cohorts). Rs117902240 was positively associated with FEV1 in children exposed to low dust mite allergen levels, but negatively associated with FEV1 in children exposed to high levels. This SNP is on chromosome 8q24, adjacent to a binding site for CCAAT/enhancer-binding protein beta, a transcription factor that forms part of the IL-17 signaling pathway. None of the SNPs identified for FEV1 /forced vital capacity replicated in the independent cohorts. Conclusions Dust mite allergen exposure modifies the estimated effect of rs117902240 on FEV1 in children with asthma. Analysis of existing data suggests that this SNP may have transcription factor regulatory functions.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>28167095</pmid><doi>10.1016/j.jaci.2016.12.967</doi><orcidid>https://orcid.org/0000-0002-9579-1591</orcidid><orcidid>https://orcid.org/0000-0001-6497-9885</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of allergy and clinical immunology, 2017-10, Vol.140 (4), p.996-1003.e7 |
| issn | 0091-6749 1097-6825 |
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| source | MEDLINE; Elsevier ScienceDirect Journals; EZB-FREE-00999 freely available EZB journals |
| subjects | Adolescent Allergens Allergies Allergy and Immunology Antigens, Dermatophagoides - immunology Asthma Asthma - immunology Case-Control Studies CCAAT-Enhancer-Binding Proteins - metabolism CCAAT/enhancer-binding protein CEBPβ Child Childhood asthma Children Children & youth Chromosome 8 Cohort Studies Cytokines Data processing Dust dust mite allergen Exposure Female Gene polymorphism gene-by-environment interactions Gene-Environment Interaction Genes Genetics Genome-Wide Association Study genome-wide interaction study Genomes Households Humans Interleukin 17 Interleukin-17 - metabolism Lung - physiology lung function Lungs Male Mites Morbidity Parents & parenting Polymorphism, Single Nucleotide Protein Binding Puerto Rico Replication Respiratory function Respiratory Function Tests Risk factors Signal transduction Single-nucleotide polymorphism Studies |
| title | Genome-wide interaction study of dust mite allergen on lung function in children with asthma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T00%3A41%3A18IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Genome-wide%20interaction%20study%20of%20dust%20mite%20allergen%20on%20lung%20function%20in%20children%20with%20asthma&rft.jtitle=Journal%20of%20allergy%20and%20clinical%20immunology&rft.au=Forno,%20Erick,%20MD,%20MPH&rft.date=2017-10-01&rft.volume=140&rft.issue=4&rft.spage=996&rft.epage=1003.e7&rft.pages=996-1003.e7&rft.issn=0091-6749&rft.eissn=1097-6825&rft_id=info:doi/10.1016/j.jaci.2016.12.967&rft_dat=%3Cproquest_pubme%3E1865821972%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1949653289&rft_id=info:pmid/28167095&rft_els_id=S0091674917301549&rfr_iscdi=true |