Association between genome-wide copy number variation and arsenic-induced skin lesions: a prospective study
Abstract Background Exposure to arsenic in drinking water is a global health problem and arsenic-induced skin lesions are hallmark of chronic arsenic toxicity. We and others have reported germline genetic variations as risk factors for such skin lesions. The role of copy number variation (CNV) in th...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2017-07-01
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| Series: | Environmental Health |
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| Online Access: | http://link.springer.com/article/10.1186/s12940-017-0283-8 |
| _version_ | 1818245979650916352 |
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| author | Muhammad G. Kibriya Farzana Jasmine Faruque Parvez Maria Argos Shantanu Roy Rachelle Paul-Brutus Tariqul Islam Alauddin Ahmed Muhammad Rakibuz-Zaman Justin Shinkle Vesna Slavkovich Joseph H. Graziano Habibul Ahsan |
| author_facet | Muhammad G. Kibriya Farzana Jasmine Faruque Parvez Maria Argos Shantanu Roy Rachelle Paul-Brutus Tariqul Islam Alauddin Ahmed Muhammad Rakibuz-Zaman Justin Shinkle Vesna Slavkovich Joseph H. Graziano Habibul Ahsan |
| author_sort | Muhammad G. Kibriya |
| collection | DOAJ |
| description | Abstract Background Exposure to arsenic in drinking water is a global health problem and arsenic-induced skin lesions are hallmark of chronic arsenic toxicity. We and others have reported germline genetic variations as risk factors for such skin lesions. The role of copy number variation (CNV) in the germline DNA in this regard is unknown. Methods From a large prospectively followed-up cohort, exposed to arsenic, we randomly selected 2171 subjects without arsenic-induced skin lesions at enrollment and genotyped their whole blood DNA samples on Illumina Cyto12v2.1 SNP chips to generate DNA copy number. Participants were followed up every 2 years for a total of 8 years, especially for the development of skin lesions. In Cox regression models, each CNV segment was used as a predictor, accounting for other potential covariates, for incidence of skin lesions. Result The presence of genomic deletion(s) in a number of genes (OR5J2, GOLGA6L7P, APBA2, GALNTL5, VN1R31P, PHKG1P2, SGCZ, ZNF658) and lincRNA genes (RP11-76I14.1, CTC-535 M15.2, RP11-73B2.2) were associated with higher risk [HR between 1.67 (CI 1.3-2.1) and 2.15 (CI 1.5-2.9) for different CNVs] for development of skin lesions independent of gender, age, and arsenic exposure. Some deletions had stronger effect in a specific gender (ZNF658 in males, SGCZ in females) and some had stronger effect in higher arsenic exposure (lincRNA CTD-3179P9.1) suggesting a possible gene-environment interaction. Conclusion This first genome-wide CNV study in a prospectively followed-up large cohort, exposed to arsenic, suggests that DNA deletion in several genes and lincRNA genes may predispose an individual to a higher risk of development of arsenic-induced skin lesions. |
| first_indexed | 2024-12-12T14:41:31Z |
| format | Article |
| id | doaj.art-dcb8f24a247d498bac9dec871ea29fac |
| institution | Directory Open Access Journal |
| issn | 1476-069X |
| language | English |
| last_indexed | 2024-12-12T14:41:31Z |
| publishDate | 2017-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Environmental Health |
| spelling | doaj.art-dcb8f24a247d498bac9dec871ea29fac2022-12-22T00:21:13ZengBMCEnvironmental Health1476-069X2017-07-0116111310.1186/s12940-017-0283-8Association between genome-wide copy number variation and arsenic-induced skin lesions: a prospective studyMuhammad G. Kibriya0Farzana Jasmine1Faruque Parvez2Maria Argos3Shantanu Roy4Rachelle Paul-Brutus5Tariqul Islam6Alauddin Ahmed7Muhammad Rakibuz-Zaman8Justin Shinkle9Vesna Slavkovich10Joseph H. Graziano11Habibul Ahsan12Department of Public Health Sciences, University of ChicagoDepartment of Public Health Sciences, University of ChicagoDepartment of Environmental Health Sciences, Mailman School of Public Health, Columbia UniversityDivision of Epidemiology and Biostatistics, School of Public Health, University of IllinoisDepartment of Public Health Sciences, University of ChicagoDepartment of Public Health Sciences, University of ChicagoUniversity of Chicago Research BangladeshUniversity of Chicago Research BangladeshUniversity of Chicago Research BangladeshDepartment of Public Health Sciences, University of ChicagoDepartment of Environmental Health Sciences, Mailman School of Public Health, Columbia UniversityDepartment of Environmental Health Sciences, Mailman School of Public Health, Columbia UniversityDepartment of Public Health Sciences, University of ChicagoAbstract Background Exposure to arsenic in drinking water is a global health problem and arsenic-induced skin lesions are hallmark of chronic arsenic toxicity. We and others have reported germline genetic variations as risk factors for such skin lesions. The role of copy number variation (CNV) in the germline DNA in this regard is unknown. Methods From a large prospectively followed-up cohort, exposed to arsenic, we randomly selected 2171 subjects without arsenic-induced skin lesions at enrollment and genotyped their whole blood DNA samples on Illumina Cyto12v2.1 SNP chips to generate DNA copy number. Participants were followed up every 2 years for a total of 8 years, especially for the development of skin lesions. In Cox regression models, each CNV segment was used as a predictor, accounting for other potential covariates, for incidence of skin lesions. Result The presence of genomic deletion(s) in a number of genes (OR5J2, GOLGA6L7P, APBA2, GALNTL5, VN1R31P, PHKG1P2, SGCZ, ZNF658) and lincRNA genes (RP11-76I14.1, CTC-535 M15.2, RP11-73B2.2) were associated with higher risk [HR between 1.67 (CI 1.3-2.1) and 2.15 (CI 1.5-2.9) for different CNVs] for development of skin lesions independent of gender, age, and arsenic exposure. Some deletions had stronger effect in a specific gender (ZNF658 in males, SGCZ in females) and some had stronger effect in higher arsenic exposure (lincRNA CTD-3179P9.1) suggesting a possible gene-environment interaction. Conclusion This first genome-wide CNV study in a prospectively followed-up large cohort, exposed to arsenic, suggests that DNA deletion in several genes and lincRNA genes may predispose an individual to a higher risk of development of arsenic-induced skin lesions.http://link.springer.com/article/10.1186/s12940-017-0283-8Copy number variationArsenicSkin lesionlincRNASurvival analysisGene-environment interaction |
| spellingShingle | Muhammad G. Kibriya Farzana Jasmine Faruque Parvez Maria Argos Shantanu Roy Rachelle Paul-Brutus Tariqul Islam Alauddin Ahmed Muhammad Rakibuz-Zaman Justin Shinkle Vesna Slavkovich Joseph H. Graziano Habibul Ahsan Association between genome-wide copy number variation and arsenic-induced skin lesions: a prospective study Environmental Health Copy number variation Arsenic Skin lesion lincRNA Survival analysis Gene-environment interaction |
| title | Association between genome-wide copy number variation and arsenic-induced skin lesions: a prospective study |
| title_full | Association between genome-wide copy number variation and arsenic-induced skin lesions: a prospective study |
| title_fullStr | Association between genome-wide copy number variation and arsenic-induced skin lesions: a prospective study |
| title_full_unstemmed | Association between genome-wide copy number variation and arsenic-induced skin lesions: a prospective study |
| title_short | Association between genome-wide copy number variation and arsenic-induced skin lesions: a prospective study |
| title_sort | association between genome wide copy number variation and arsenic induced skin lesions a prospective study |
| topic | Copy number variation Arsenic Skin lesion lincRNA Survival analysis Gene-environment interaction |
| url | http://link.springer.com/article/10.1186/s12940-017-0283-8 |
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