Orofacial Cleft Risk Is Increased with Maternal Smoking and Specific Detoxification-Gene Variants
Maternal smoking is a recognized risk factor for orofacial clefts. Maternal or fetal pharmacogenetic variants are plausible modulators of this risk. In this work, we studied 5,427 DNA samples, including 1,244 from subjects in Denmark and Iowa with facial clefting and 4,183 from parents, siblings, or...
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| Veröffentlicht in: | American journal of human genetics 2007-01, Vol.80 (1), p.76-90 |
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| creator | Shi, Min Christensen, Kaare Weinberg, Clarice R. Romitti, Paul Bathum, Lise Lozada, Anthony Morris, Richard W. Lovett, Michael Murray, Jeffrey C. |
| description | Maternal smoking is a recognized risk factor for orofacial clefts. Maternal or fetal pharmacogenetic variants are plausible modulators of this risk. In this work, we studied 5,427 DNA samples, including 1,244 from subjects in Denmark and Iowa with facial clefting and 4,183 from parents, siblings, or unrelated population controls. We examined 25 single-nucleotide polymorphisms in 16 genes in pathways for detoxification of components of cigarette smoke, to look for evidence of gene-environment interactions. For genes identified as related to oral clefting, we studied gene-expression profiles in fetal development in the relevant tissues and time intervals. Maternal smoking was a significant risk factor for clefting and showed dosage effects, in both the Danish and Iowan data. Suggestive effects of variants in the fetal
NAT2 and
CYP1A1 genes were observed in both the Iowan and the Danish participants. In an expanded case set,
NAT2 continued to show significant overtransmission of an allele to the fetus, with a final
P value of .00003. There was an interaction between maternal smoking and fetal inheritance of a
GSTT1-null deletion, seen in both the Danish (
P=.03) and Iowan (
P=.002) studies, with a Fisher’s combined
P value of |
| doi_str_mv | 10.1086/510518 |
| format | Article |
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NAT2 and
CYP1A1 genes were observed in both the Iowan and the Danish participants. In an expanded case set,
NAT2 continued to show significant overtransmission of an allele to the fetus, with a final
P value of .00003. There was an interaction between maternal smoking and fetal inheritance of a
GSTT1-null deletion, seen in both the Danish (
P=.03) and Iowan (
P=.002) studies, with a Fisher’s combined
P value of <.001, which remained significant after correction for multiple comparisons. Gene-expression analysis demonstrated expression of
GSTT1 in human embryonic craniofacial tissues during the relevant developmental interval. This study benefited from two large samples, involving independent populations, that provided substantial power and a framework for future studies that could identify a susceptible population for preventive health care.</description><identifier>ISSN: 0002-9297</identifier><identifier>EISSN: 1537-6605</identifier><identifier>DOI: 10.1086/510518</identifier><identifier>PMID: 17160896</identifier><identifier>CODEN: AJHGAG</identifier><language>eng</language><publisher>Chicago, IL: Elsevier Inc</publisher><subject>Arylamine N-Acetyltransferase - biosynthesis ; Arylamine N-Acetyltransferase - genetics ; Biological and medical sciences ; Cleft Lip - genetics ; Cleft Palate - genetics ; Cytochrome P-450 CYP1A1 - biosynthesis ; Cytochrome P-450 CYP1A1 - genetics ; Deoxyribonucleic acid ; DNA ; Embryo, Mammalian - metabolism ; Face ; Female ; Fundamental and applied biological sciences. Psychology ; Gene expression ; Gene Expression Profiling ; General aspects. Genetic counseling ; Genetics of eukaryotes. Biological and molecular evolution ; Glutathione Transferase - genetics ; History, 16th Century ; Humans ; Linkage Disequilibrium ; Male ; Maternal Exposure - adverse effects ; Medical genetics ; Medical sciences ; Molecular and cellular biology ; Polymorphism ; Polymorphism, Single Nucleotide ; Pregnancy ; Risk Factors ; Smoking ; Smoking - genetics ; Tobacco, tobacco smoking ; Toxicology</subject><ispartof>American journal of human genetics, 2007-01, Vol.80 (1), p.76-90</ispartof><rights>2007 The American Society of Human Genetics</rights><rights>2007 INIST-CNRS</rights><rights>Copyright University of Chicago, acting through its Press Jan 2007</rights><rights>2006 by The American Society of Human Genetics. All rights reserved. 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c493t-3386eaaa78c9282f9f77e9e7484f6348771f9f9f6f2a282ccfa497ec190ca83c3</citedby><cites>FETCH-LOGICAL-c493t-3386eaaa78c9282f9f77e9e7484f6348771f9f9f6f2a282ccfa497ec190ca83c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1785306/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://dx.doi.org/10.1086/510518$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,3550,27924,27925,45995,53791,53793</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18380913$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17160896$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shi, Min</creatorcontrib><creatorcontrib>Christensen, Kaare</creatorcontrib><creatorcontrib>Weinberg, Clarice R.</creatorcontrib><creatorcontrib>Romitti, Paul</creatorcontrib><creatorcontrib>Bathum, Lise</creatorcontrib><creatorcontrib>Lozada, Anthony</creatorcontrib><creatorcontrib>Morris, Richard W.</creatorcontrib><creatorcontrib>Lovett, Michael</creatorcontrib><creatorcontrib>Murray, Jeffrey C.</creatorcontrib><title>Orofacial Cleft Risk Is Increased with Maternal Smoking and Specific Detoxification-Gene Variants</title><title>American journal of human genetics</title><addtitle>Am J Hum Genet</addtitle><description>Maternal smoking is a recognized risk factor for orofacial clefts. Maternal or fetal pharmacogenetic variants are plausible modulators of this risk. In this work, we studied 5,427 DNA samples, including 1,244 from subjects in Denmark and Iowa with facial clefting and 4,183 from parents, siblings, or unrelated population controls. We examined 25 single-nucleotide polymorphisms in 16 genes in pathways for detoxification of components of cigarette smoke, to look for evidence of gene-environment interactions. For genes identified as related to oral clefting, we studied gene-expression profiles in fetal development in the relevant tissues and time intervals. Maternal smoking was a significant risk factor for clefting and showed dosage effects, in both the Danish and Iowan data. Suggestive effects of variants in the fetal
NAT2 and
CYP1A1 genes were observed in both the Iowan and the Danish participants. In an expanded case set,
NAT2 continued to show significant overtransmission of an allele to the fetus, with a final
P value of .00003. There was an interaction between maternal smoking and fetal inheritance of a
GSTT1-null deletion, seen in both the Danish (
P=.03) and Iowan (
P=.002) studies, with a Fisher’s combined
P value of <.001, which remained significant after correction for multiple comparisons. Gene-expression analysis demonstrated expression of
GSTT1 in human embryonic craniofacial tissues during the relevant developmental interval. This study benefited from two large samples, involving independent populations, that provided substantial power and a framework for future studies that could identify a susceptible population for preventive health care.</description><subject>Arylamine N-Acetyltransferase - biosynthesis</subject><subject>Arylamine N-Acetyltransferase - genetics</subject><subject>Biological and medical sciences</subject><subject>Cleft Lip - genetics</subject><subject>Cleft Palate - genetics</subject><subject>Cytochrome P-450 CYP1A1 - biosynthesis</subject><subject>Cytochrome P-450 CYP1A1 - genetics</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Embryo, Mammalian - metabolism</subject><subject>Face</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>General aspects. Genetic counseling</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Glutathione Transferase - genetics</subject><subject>History, 16th Century</subject><subject>Humans</subject><subject>Linkage Disequilibrium</subject><subject>Male</subject><subject>Maternal Exposure - adverse effects</subject><subject>Medical genetics</subject><subject>Medical sciences</subject><subject>Molecular and cellular biology</subject><subject>Polymorphism</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Pregnancy</subject><subject>Risk Factors</subject><subject>Smoking</subject><subject>Smoking - genetics</subject><subject>Tobacco, tobacco smoking</subject><subject>Toxicology</subject><issn>0002-9297</issn><issn>1537-6605</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkdFPFDEQxhsjkRP1TzCNib6ttNvdbftiYk7BSyAkoL42Y3cKhb32aHso_7293EWQp5nM_PLN5PsIecPZR87UcNhz1nP1jMx4L2QzDKx_TmaMsbbRrZb75GXO14xxrph4Qfa55ANTepgROEvRgfUw0fmErtBzn2_oItNFsAkh40h_-3JFT6FgCpW6WMYbHy4phJFerNB65y39giX-2XRQfAzNMQakPyF5CCW_InsOpoyvd_WA_Dj6-n3-rTk5O17MP580ttOiNEKoAQFAKqtb1TrtpESNslOdG0SnpOR1pt3gWqh7ax10WqLlmllQwooD8mmru1r_WuJoMZQEk1klv4R0byJ48_8m-CtzGe8Ml6oXbKgCH3YCKd6uMRez9NniNEHAuM6G605Xz7oKvnsCXsf1xpxsWq6r9YI_UrMp5pzQ_fuEM7OJzGwjq-Dbx38_YLuMKvB-B0C2MLkEwfr8wCmhmOaicmzLYXX5zmMy2XoMFkef0BYzRv_09l-Vjq4M</recordid><startdate>20070101</startdate><enddate>20070101</enddate><creator>Shi, Min</creator><creator>Christensen, Kaare</creator><creator>Weinberg, Clarice R.</creator><creator>Romitti, Paul</creator><creator>Bathum, Lise</creator><creator>Lozada, Anthony</creator><creator>Morris, Richard W.</creator><creator>Lovett, Michael</creator><creator>Murray, Jeffrey C.</creator><general>Elsevier Inc</general><general>University of Chicago Press</general><general>Cell Press</general><general>The American Society of Human Genetics</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><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>7QP</scope><scope>7TK</scope><scope>7TM</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20070101</creationdate><title>Orofacial Cleft Risk Is Increased with Maternal Smoking and Specific Detoxification-Gene Variants</title><author>Shi, Min ; Christensen, Kaare ; Weinberg, Clarice R. ; Romitti, Paul ; Bathum, Lise ; Lozada, Anthony ; Morris, Richard W. ; Lovett, Michael ; Murray, Jeffrey C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c493t-3386eaaa78c9282f9f77e9e7484f6348771f9f9f6f2a282ccfa497ec190ca83c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Arylamine N-Acetyltransferase - biosynthesis</topic><topic>Arylamine N-Acetyltransferase - genetics</topic><topic>Biological and medical sciences</topic><topic>Cleft Lip - genetics</topic><topic>Cleft Palate - genetics</topic><topic>Cytochrome P-450 CYP1A1 - biosynthesis</topic><topic>Cytochrome P-450 CYP1A1 - genetics</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Embryo, Mammalian - metabolism</topic><topic>Face</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>General aspects. Genetic counseling</topic><topic>Genetics of eukaryotes. Biological and molecular evolution</topic><topic>Glutathione Transferase - genetics</topic><topic>History, 16th Century</topic><topic>Humans</topic><topic>Linkage Disequilibrium</topic><topic>Male</topic><topic>Maternal Exposure - adverse effects</topic><topic>Medical genetics</topic><topic>Medical sciences</topic><topic>Molecular and cellular biology</topic><topic>Polymorphism</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Pregnancy</topic><topic>Risk Factors</topic><topic>Smoking</topic><topic>Smoking - genetics</topic><topic>Tobacco, tobacco smoking</topic><topic>Toxicology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shi, Min</creatorcontrib><creatorcontrib>Christensen, Kaare</creatorcontrib><creatorcontrib>Weinberg, Clarice R.</creatorcontrib><creatorcontrib>Romitti, Paul</creatorcontrib><creatorcontrib>Bathum, Lise</creatorcontrib><creatorcontrib>Lozada, Anthony</creatorcontrib><creatorcontrib>Morris, Richard W.</creatorcontrib><creatorcontrib>Lovett, Michael</creatorcontrib><creatorcontrib>Murray, Jeffrey C.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>American journal of human genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shi, Min</au><au>Christensen, Kaare</au><au>Weinberg, Clarice R.</au><au>Romitti, Paul</au><au>Bathum, Lise</au><au>Lozada, Anthony</au><au>Morris, Richard W.</au><au>Lovett, Michael</au><au>Murray, Jeffrey C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Orofacial Cleft Risk Is Increased with Maternal Smoking and Specific Detoxification-Gene Variants</atitle><jtitle>American journal of human genetics</jtitle><addtitle>Am J Hum Genet</addtitle><date>2007-01-01</date><risdate>2007</risdate><volume>80</volume><issue>1</issue><spage>76</spage><epage>90</epage><pages>76-90</pages><issn>0002-9297</issn><eissn>1537-6605</eissn><coden>AJHGAG</coden><abstract>Maternal smoking is a recognized risk factor for orofacial clefts. Maternal or fetal pharmacogenetic variants are plausible modulators of this risk. In this work, we studied 5,427 DNA samples, including 1,244 from subjects in Denmark and Iowa with facial clefting and 4,183 from parents, siblings, or unrelated population controls. We examined 25 single-nucleotide polymorphisms in 16 genes in pathways for detoxification of components of cigarette smoke, to look for evidence of gene-environment interactions. For genes identified as related to oral clefting, we studied gene-expression profiles in fetal development in the relevant tissues and time intervals. Maternal smoking was a significant risk factor for clefting and showed dosage effects, in both the Danish and Iowan data. Suggestive effects of variants in the fetal
NAT2 and
CYP1A1 genes were observed in both the Iowan and the Danish participants. In an expanded case set,
NAT2 continued to show significant overtransmission of an allele to the fetus, with a final
P value of .00003. There was an interaction between maternal smoking and fetal inheritance of a
GSTT1-null deletion, seen in both the Danish (
P=.03) and Iowan (
P=.002) studies, with a Fisher’s combined
P value of <.001, which remained significant after correction for multiple comparisons. Gene-expression analysis demonstrated expression of
GSTT1 in human embryonic craniofacial tissues during the relevant developmental interval. This study benefited from two large samples, involving independent populations, that provided substantial power and a framework for future studies that could identify a susceptible population for preventive health care.</abstract><cop>Chicago, IL</cop><pub>Elsevier Inc</pub><pmid>17160896</pmid><doi>10.1086/510518</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | American journal of human genetics, 2007-01, Vol.80 (1), p.76-90 |
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| source | MEDLINE; Cell Press Free Archives; ScienceDirect Journals (5 years ago - present); EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Arylamine N-Acetyltransferase - biosynthesis Arylamine N-Acetyltransferase - genetics Biological and medical sciences Cleft Lip - genetics Cleft Palate - genetics Cytochrome P-450 CYP1A1 - biosynthesis Cytochrome P-450 CYP1A1 - genetics Deoxyribonucleic acid DNA Embryo, Mammalian - metabolism Face Female Fundamental and applied biological sciences. Psychology Gene expression Gene Expression Profiling General aspects. Genetic counseling Genetics of eukaryotes. Biological and molecular evolution Glutathione Transferase - genetics History, 16th Century Humans Linkage Disequilibrium Male Maternal Exposure - adverse effects Medical genetics Medical sciences Molecular and cellular biology Polymorphism Polymorphism, Single Nucleotide Pregnancy Risk Factors Smoking Smoking - genetics Tobacco, tobacco smoking Toxicology |
| title | Orofacial Cleft Risk Is Increased with Maternal Smoking and Specific Detoxification-Gene Variants |
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