Associations between Variation in CHRNA5-CHRNA3-CHRNB4, Body Mass Index and Blood Pressure in the Northern Finland Birth Cohort 1966 英文参考文献.docVIP

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Associations between Variation in CHRNA5-CHRNA3-CHRNB4, Body Mass Index and Blood Pressure in the Northern Finland Birth Cohort 1966 英文参考文献.doc

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Associations between Variation in CHRNA5-CHRNA3-CHRNB4, Body Mass Index and Blood Pressure in the Northern Finland Birth Cohort 1966 英文参考文献

AssociationsbetweenVariationinCHRNA5-CHRNA3- CHRNB4,BodyMassIndexandBloodPressureinthe NorthernFinlandBirthCohort1966 MarikaKaakinen1,2*,FrancescaDucci3,4,MikkoJ.Sillanpa¨a¨2,5,6,EsaLa¨a¨ra¨5,Marjo-RiittaJa¨rvelin1,2,7,8 1InstituteofHealthSciences,UniversityofOulu,Oulu,Finland,2BiocenterOulu,Oulu,Finland,3PsychologicalMedicine,InstituteofPsychiatry,King’sCollege,London, UnitedKingdom,4DivisionofMentalHealth,St.George’sUniversityofLondon,London,UnitedKingdom,5DepartmentofMathematicalSciences,UniversityofOulu, Oulu, Finland, 6Department of Biology, University of Oulu, Oulu, Finland, 7Department of Life Course and Services, National Institute for Health and Welfare, Oulu, Finland,8DepartmentofEpidemiologyandBiostatistics,MRC-HPACentreforEnvironmentandHealth,ImperialCollegeLondon,London,UnitedKingdom Abstract Background:TheCHRNA5-CHRNA3-CHRNB4geneclusteron15q25hasconsistentlybeenassociatedwithsmokingquantity, nicotinedependenceandlungcancer.Recentresearchalsopointstowardsitsinvolvementincardiovascularhomeostasis, butstudiesinlargehumansamplesarelacking,especiallyontheroleofthegeneclusterinbloodpressureregulation. Methodology/Principal Findings: We studied the associations between 18 single nucleotide polymorphisms (SNPs) in CHRNA5-CHRNA3-CHRNB4andsystolicbloodpressure(SBP),diastolicbloodpressure(DBP),andbodymassindex(BMI)in 5402youngadultsfromtheNorthernFinlandBirthCohort1966.Weobservedsomeevidenceforassociationsbetweentwo SNPsandSBPandbetweensixSNPsandBMI;theevidenceforassociationswithDBPwasweaker.Theassociationswiththe threephenotypesweredrivenbydifferentlociwithlowlinkagedisequilibriumwitheachother.Theassociationsappeared morepronouncedinsmokers,suchthatthesmoking-increasingalleleswouldpredictlowerSBPandBMI.Eachadditional copyofthers1948G-alleleandthers950776A-allelereducedSBPonaverageby21.21(95%CI22.01,20.40)mmHgin smokers.ThevariantsassociatedwithBMIincludedrs2036534,rs6495309,rs1996371,rs6495314,rs4887077andrandhadanaverageeffectsizeof20.38(20.68,20.08)k