Association between Variants of the Leptin Receptor Gene (LEPR) and Overweight A Systematic Review and an Analysis of the CoLaus Study 英文参考文献.docVIP

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Association between Variants of the Leptin Receptor Gene (LEPR) and Overweight A Systematic Review and an Analysis of the CoLaus Study 英文参考文献.doc

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Association between Variants of the Leptin Receptor Gene (LEPR) and Overweight A Systematic Review and an Analysis of the CoLaus Study 英文参考文献

AssociationbetweenVariantsoftheLeptinReceptor Gene(LEPR)andOverweight:ASystematicReviewand anAnalysisoftheCoLausStudy NicoleBender1,2*,Noe¨miAllemann1,DianaMarek3,PeterVollenweider4,Ge′rardWaeber4 ,Vincent Mooser5,MatthiasEgger1,MurielleBochud6 1InstituteofSocialandPreventiveMedicine,UniversityofBern,Bern,Switzerland,2InstituteforHumanEvolution,UniversityoftheWitwatersrand,Johannesburg,South Africa,3DepartmentofMedicalGenetics,SwissInstituteofBioinformatics,UniversityofLausanne,Switzerland,Lausanne,Switzerland,4DepartmentofMedicine,Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, 5GlaxoSmithKline, Philadelphia, Pennsylvania, United States of America, 6Institute of Social and Preventive Medicine,CentreHospitalierUniversitaireVaudois,UniversityofLausanne,Lausanne,Switzerland Abstract Background:Threenon-synonymoussinglenucleotidepolymorphisms(Q223R,K109RandK656N)oftheleptinreceptor gene (LEPR) have been tested for association with obesity-related outcomes in multiple studies, showing inconclusive results. We performed a systematic review and meta-analysis on the association of the three LEPR variants with BMI. In addition,weanalysed15SNPswithintheLEPRgeneintheCoLausstudy,assessingtheinteractionofthevariantswithsex. Methodology/PrincipalFindings:Wesearchedelectronicdatabases,includingpopulation-basedstudiesthatinvestigated the association between LEPR variants Q223R, K109R and K656N and obesity- related phenotypes in healthy, unrelated subjects.Wefurthermoreperformedmeta-analysesofthegenotypeandallelefrequenciesincase-controlstudies.Results werestratifiedbySNPandbypotentialeffectmodifiers.CoLausdatawereanalysedbylogisticandlinearregressionsand testedforinteractionwithsex.Themeta-analysisofpublisheddatadidnotshowanoverallassociationbetweenanyofthe tested LEPR variants and overweight. However, the choice of a BMI cut-off value to distinguish cases from controls was crucialtoexplainheterogeneityinQ223R.Differencesinallelefrequenciesacrossethnicgroupsarec