NOS3 polymorphisms, cigarette smoking, and cardiovascular disease risk: The Atherosclerosis Risk in Communities study
OBJECTIVEEndothelial nitric oxide synthase (NOS3) activity and cigarette smoking significantly influence endothelial function. We sought to determine whether cigarette smoking modified the association between NOS3 polymorphisms and risk of coronary heart disease or stroke. METHODSAll 1085 incident c...
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| creator | Lee, Craig R North, Kari E Bray, Molly S Avery, Christy L Mosher, Mary Jane Couper, David J Coresh, Josef Folsom, Aaron R Boerwinkle, Eric Heiss, Gerardo Zeldin, Darryl C |
| description | OBJECTIVEEndothelial nitric oxide synthase (NOS3) activity and cigarette smoking significantly influence endothelial function. We sought to determine whether cigarette smoking modified the association between NOS3 polymorphisms and risk of coronary heart disease or stroke.
METHODSAll 1085 incident coronary heart disease cases, all 300 incident ischemic stroke cases, and 1065 reference individuals from the Atherosclerosis Risk in Communities study were genotyped for the T-786C and E298D polymorphisms in NOS3. Using a case–cohort design, associations between genotype/haplotype and disease risk were evaluated by multivariable proportional hazards regression. Multiplicative scale interaction testing evaluated the influence of cigarette smoking history at baseline on these associations.
RESULTSIn Caucasians, association between E298D genotype and risk of coronary heart disease was significantly modified by current smoking status (interaction P=0.013), with the highest risk observed in smokers carrying the variant D298 allele relative to nonsmokers carrying two E298 alleles (adjusted hazard rate ratio 2.07, 95% confidence interval 1.39–3.07). In African-Americans, association between T-786C genotype and risk of ischemic stroke was significantly modified by pack-year smoking history (interaction P=0.037), with the highest risk observed in ≥20 pack-year smokers carrying the variant C-786 allele relative to |
| doi_str_mv | 10.1097/01.fpc.0000236324.96056.16 |
| format | Article |
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METHODSAll 1085 incident coronary heart disease cases, all 300 incident ischemic stroke cases, and 1065 reference individuals from the Atherosclerosis Risk in Communities study were genotyped for the T-786C and E298D polymorphisms in NOS3. Using a case–cohort design, associations between genotype/haplotype and disease risk were evaluated by multivariable proportional hazards regression. Multiplicative scale interaction testing evaluated the influence of cigarette smoking history at baseline on these associations.
RESULTSIn Caucasians, association between E298D genotype and risk of coronary heart disease was significantly modified by current smoking status (interaction P=0.013), with the highest risk observed in smokers carrying the variant D298 allele relative to nonsmokers carrying two E298 alleles (adjusted hazard rate ratio 2.07, 95% confidence interval 1.39–3.07). In African-Americans, association between T-786C genotype and risk of ischemic stroke was significantly modified by pack-year smoking history (interaction P=0.037), with the highest risk observed in ≥20 pack-year smokers carrying the variant C-786 allele relative to <20 pack-year smokers carrying two T-786 alleles (adjusted hazard rate ratio 4.03, 95% confidence interval 1.54–10.6).
CONCLUSIONSAn interaction between the E298D and T-786C polymorphisms in NOS3, cigarette smoking, and risk of incident coronary heart disease and ischemic stroke events appears to exist, suggesting a potential complex interplay between genetic and environmental factors and cardiovascular disease risk.</description><identifier>ISSN: 1744-6872</identifier><identifier>EISSN: 1744-6880</identifier><identifier>DOI: 10.1097/01.fpc.0000236324.96056.16</identifier><identifier>PMID: 17108813</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins, Inc</publisher><subject>African Americans - genetics ; Alleles ; Atherosclerosis (general aspects, experimental research) ; Base Sequence ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Cardiovascular Diseases - enzymology ; Cardiovascular Diseases - epidemiology ; Cardiovascular Diseases - etiology ; Cardiovascular Diseases - genetics ; Cohort Studies ; Coronary Disease - enzymology ; Coronary Disease - epidemiology ; Coronary Disease - etiology ; Coronary Disease - genetics ; DNA Primers - genetics ; European Continental Ancestry Group - genetics ; Female ; General pharmacology ; Genotype ; Haplotypes ; Humans ; Longitudinal Studies ; Male ; Medical sciences ; Middle Aged ; Nitric Oxide Synthase Type III - genetics ; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions ; Pharmacology. Drug treatments ; Polymorphism, Single Nucleotide ; Proportional Hazards Models ; Risk Factors ; Smoking - adverse effects ; Stroke - enzymology ; Stroke - epidemiology ; Stroke - etiology ; Stroke - genetics ; Tobacco, tobacco smoking ; Toxicology ; United States - epidemiology</subject><ispartof>Pharmacogenetics and genomics, 2006-12, Vol.16 (12), p.891-899</ispartof><rights>2006 Lippincott Williams & Wilkins, Inc.</rights><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5656-980269371ec94a982f8474a6932ac162d55701209ce42d1a062589604f2575ee3</citedby><cites>FETCH-LOGICAL-c5656-980269371ec94a982f8474a6932ac162d55701209ce42d1a062589604f2575ee3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,781,785,886,27929,27930</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18326573$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17108813$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Craig R</creatorcontrib><creatorcontrib>North, Kari E</creatorcontrib><creatorcontrib>Bray, Molly S</creatorcontrib><creatorcontrib>Avery, Christy L</creatorcontrib><creatorcontrib>Mosher, Mary Jane</creatorcontrib><creatorcontrib>Couper, David J</creatorcontrib><creatorcontrib>Coresh, Josef</creatorcontrib><creatorcontrib>Folsom, Aaron R</creatorcontrib><creatorcontrib>Boerwinkle, Eric</creatorcontrib><creatorcontrib>Heiss, Gerardo</creatorcontrib><creatorcontrib>Zeldin, Darryl C</creatorcontrib><title>NOS3 polymorphisms, cigarette smoking, and cardiovascular disease risk: The Atherosclerosis Risk in Communities study</title><title>Pharmacogenetics and genomics</title><addtitle>Pharmacogenet Genomics</addtitle><description>OBJECTIVEEndothelial nitric oxide synthase (NOS3) activity and cigarette smoking significantly influence endothelial function. We sought to determine whether cigarette smoking modified the association between NOS3 polymorphisms and risk of coronary heart disease or stroke.
METHODSAll 1085 incident coronary heart disease cases, all 300 incident ischemic stroke cases, and 1065 reference individuals from the Atherosclerosis Risk in Communities study were genotyped for the T-786C and E298D polymorphisms in NOS3. Using a case–cohort design, associations between genotype/haplotype and disease risk were evaluated by multivariable proportional hazards regression. Multiplicative scale interaction testing evaluated the influence of cigarette smoking history at baseline on these associations.
RESULTSIn Caucasians, association between E298D genotype and risk of coronary heart disease was significantly modified by current smoking status (interaction P=0.013), with the highest risk observed in smokers carrying the variant D298 allele relative to nonsmokers carrying two E298 alleles (adjusted hazard rate ratio 2.07, 95% confidence interval 1.39–3.07). In African-Americans, association between T-786C genotype and risk of ischemic stroke was significantly modified by pack-year smoking history (interaction P=0.037), with the highest risk observed in ≥20 pack-year smokers carrying the variant C-786 allele relative to <20 pack-year smokers carrying two T-786 alleles (adjusted hazard rate ratio 4.03, 95% confidence interval 1.54–10.6).
CONCLUSIONSAn interaction between the E298D and T-786C polymorphisms in NOS3, cigarette smoking, and risk of incident coronary heart disease and ischemic stroke events appears to exist, suggesting a potential complex interplay between genetic and environmental factors and cardiovascular disease risk.</description><subject>African Americans - genetics</subject><subject>Alleles</subject><subject>Atherosclerosis (general aspects, experimental research)</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>Cardiovascular Diseases - enzymology</subject><subject>Cardiovascular Diseases - epidemiology</subject><subject>Cardiovascular Diseases - etiology</subject><subject>Cardiovascular Diseases - genetics</subject><subject>Cohort Studies</subject><subject>Coronary Disease - enzymology</subject><subject>Coronary Disease - epidemiology</subject><subject>Coronary Disease - etiology</subject><subject>Coronary Disease - genetics</subject><subject>DNA Primers - genetics</subject><subject>European Continental Ancestry Group - genetics</subject><subject>Female</subject><subject>General pharmacology</subject><subject>Genotype</subject><subject>Haplotypes</subject><subject>Humans</subject><subject>Longitudinal Studies</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Nitric Oxide Synthase Type III - genetics</subject><subject>Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions</subject><subject>Pharmacology. Drug treatments</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Proportional Hazards Models</subject><subject>Risk Factors</subject><subject>Smoking - adverse effects</subject><subject>Stroke - enzymology</subject><subject>Stroke - epidemiology</subject><subject>Stroke - etiology</subject><subject>Stroke - genetics</subject><subject>Tobacco, tobacco smoking</subject><subject>Toxicology</subject><subject>United States - epidemiology</subject><issn>1744-6872</issn><issn>1744-6880</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkd1u1DAQhSMEoqXwCshCgqsm-Cd27F4gVSsKSBWVoFxbxplszDpxaiet9u3rZVdd8IU98nwzHp9TFO8IrghWzUdMqm6yFc6LMsFoXSmBuaiIeFackqauSyElfv4UN_SkeJXSH4yZUDV9WZyQhmApCTstlu83Pxmagt8OIU69S0M6R9atTYR5BpSGsHHj-hyZsUXWxNaFe5Ps4k1ErUtgEqDo0uYC3faALuceYkjW73aX0I-cQW5EqzAMy-hmBwmleWm3r4sXnfEJ3hzOs-LX1efb1dfy-ubLt9XldWm54KJUElOhWEPAqtooSTtZN7XJV9RYImjLeYMJxcpCTVtisKBcZi3qjvKGA7Cz4tO-77T8HqC1MM7ReD1FN5i41cE4_X9mdL1eh3tNVCOzernBh0ODGO4WSLMeXLLgvRkhLEkLSThXimXwYg_a_PUUoXt6hGC9c01jorNr-uia_uuaJiIXv_13zGPpwaYMvD8AWXzju2hG69KRk4wK3uy4es89BD9DTBu_PEDUPRg_93kCShgmpKQYiywbxuVuGsEeAZ-vsiU</recordid><startdate>200612</startdate><enddate>200612</enddate><creator>Lee, Craig R</creator><creator>North, Kari E</creator><creator>Bray, Molly S</creator><creator>Avery, Christy L</creator><creator>Mosher, Mary Jane</creator><creator>Couper, David J</creator><creator>Coresh, Josef</creator><creator>Folsom, Aaron R</creator><creator>Boerwinkle, Eric</creator><creator>Heiss, Gerardo</creator><creator>Zeldin, Darryl C</creator><general>Lippincott Williams & Wilkins, Inc</general><general>Lippincott Williams and Wilkins</general><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>7X8</scope><scope>5PM</scope></search><sort><creationdate>200612</creationdate><title>NOS3 polymorphisms, cigarette smoking, and cardiovascular disease risk: The Atherosclerosis Risk in Communities study</title><author>Lee, Craig R ; North, Kari E ; Bray, Molly S ; Avery, Christy L ; Mosher, Mary Jane ; Couper, David J ; Coresh, Josef ; Folsom, Aaron R ; Boerwinkle, Eric ; Heiss, Gerardo ; Zeldin, Darryl C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5656-980269371ec94a982f8474a6932ac162d55701209ce42d1a062589604f2575ee3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>African Americans - genetics</topic><topic>Alleles</topic><topic>Atherosclerosis (general aspects, experimental research)</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Cardiology. Vascular system</topic><topic>Cardiovascular Diseases - enzymology</topic><topic>Cardiovascular Diseases - epidemiology</topic><topic>Cardiovascular Diseases - etiology</topic><topic>Cardiovascular Diseases - genetics</topic><topic>Cohort Studies</topic><topic>Coronary Disease - enzymology</topic><topic>Coronary Disease - epidemiology</topic><topic>Coronary Disease - etiology</topic><topic>Coronary Disease - genetics</topic><topic>DNA Primers - genetics</topic><topic>European Continental Ancestry Group - genetics</topic><topic>Female</topic><topic>General pharmacology</topic><topic>Genotype</topic><topic>Haplotypes</topic><topic>Humans</topic><topic>Longitudinal Studies</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Nitric Oxide Synthase Type III - genetics</topic><topic>Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions</topic><topic>Pharmacology. Drug treatments</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Proportional Hazards Models</topic><topic>Risk Factors</topic><topic>Smoking - adverse effects</topic><topic>Stroke - enzymology</topic><topic>Stroke - epidemiology</topic><topic>Stroke - etiology</topic><topic>Stroke - genetics</topic><topic>Tobacco, tobacco smoking</topic><topic>Toxicology</topic><topic>United States - epidemiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Craig R</creatorcontrib><creatorcontrib>North, Kari E</creatorcontrib><creatorcontrib>Bray, Molly S</creatorcontrib><creatorcontrib>Avery, Christy L</creatorcontrib><creatorcontrib>Mosher, Mary Jane</creatorcontrib><creatorcontrib>Couper, David J</creatorcontrib><creatorcontrib>Coresh, Josef</creatorcontrib><creatorcontrib>Folsom, Aaron R</creatorcontrib><creatorcontrib>Boerwinkle, Eric</creatorcontrib><creatorcontrib>Heiss, Gerardo</creatorcontrib><creatorcontrib>Zeldin, Darryl C</creatorcontrib><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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Pharmacogenetics and genomics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Craig R</au><au>North, Kari E</au><au>Bray, Molly S</au><au>Avery, Christy L</au><au>Mosher, Mary Jane</au><au>Couper, David J</au><au>Coresh, Josef</au><au>Folsom, Aaron R</au><au>Boerwinkle, Eric</au><au>Heiss, Gerardo</au><au>Zeldin, Darryl C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>NOS3 polymorphisms, cigarette smoking, and cardiovascular disease risk: The Atherosclerosis Risk in Communities study</atitle><jtitle>Pharmacogenetics and genomics</jtitle><addtitle>Pharmacogenet Genomics</addtitle><date>2006-12</date><risdate>2006</risdate><volume>16</volume><issue>12</issue><spage>891</spage><epage>899</epage><pages>891-899</pages><issn>1744-6872</issn><eissn>1744-6880</eissn><abstract>OBJECTIVEEndothelial nitric oxide synthase (NOS3) activity and cigarette smoking significantly influence endothelial function. We sought to determine whether cigarette smoking modified the association between NOS3 polymorphisms and risk of coronary heart disease or stroke.
METHODSAll 1085 incident coronary heart disease cases, all 300 incident ischemic stroke cases, and 1065 reference individuals from the Atherosclerosis Risk in Communities study were genotyped for the T-786C and E298D polymorphisms in NOS3. Using a case–cohort design, associations between genotype/haplotype and disease risk were evaluated by multivariable proportional hazards regression. Multiplicative scale interaction testing evaluated the influence of cigarette smoking history at baseline on these associations.
RESULTSIn Caucasians, association between E298D genotype and risk of coronary heart disease was significantly modified by current smoking status (interaction P=0.013), with the highest risk observed in smokers carrying the variant D298 allele relative to nonsmokers carrying two E298 alleles (adjusted hazard rate ratio 2.07, 95% confidence interval 1.39–3.07). In African-Americans, association between T-786C genotype and risk of ischemic stroke was significantly modified by pack-year smoking history (interaction P=0.037), with the highest risk observed in ≥20 pack-year smokers carrying the variant C-786 allele relative to <20 pack-year smokers carrying two T-786 alleles (adjusted hazard rate ratio 4.03, 95% confidence interval 1.54–10.6).
CONCLUSIONSAn interaction between the E298D and T-786C polymorphisms in NOS3, cigarette smoking, and risk of incident coronary heart disease and ischemic stroke events appears to exist, suggesting a potential complex interplay between genetic and environmental factors and cardiovascular disease risk.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins, Inc</pub><pmid>17108813</pmid><doi>10.1097/01.fpc.0000236324.96056.16</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | African Americans - genetics Alleles Atherosclerosis (general aspects, experimental research) Base Sequence Biological and medical sciences Blood and lymphatic vessels Cardiology. Vascular system Cardiovascular Diseases - enzymology Cardiovascular Diseases - epidemiology Cardiovascular Diseases - etiology Cardiovascular Diseases - genetics Cohort Studies Coronary Disease - enzymology Coronary Disease - epidemiology Coronary Disease - etiology Coronary Disease - genetics DNA Primers - genetics European Continental Ancestry Group - genetics Female General pharmacology Genotype Haplotypes Humans Longitudinal Studies Male Medical sciences Middle Aged Nitric Oxide Synthase Type III - genetics Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions Pharmacology. Drug treatments Polymorphism, Single Nucleotide Proportional Hazards Models Risk Factors Smoking - adverse effects Stroke - enzymology Stroke - epidemiology Stroke - etiology Stroke - genetics Tobacco, tobacco smoking Toxicology United States - epidemiology |
| title | NOS3 polymorphisms, cigarette smoking, and cardiovascular disease risk: The Atherosclerosis Risk in Communities study |
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