Association of LIN28B with Adult Adiposity-Related Traits in Females 英文参考文献.docVIP

AssociationofLIN28BwithAdultAdiposity-Related TraitsinFemales JaakkoT.Leinonen1,IdaSurakka1,2,AkiS.Havulinna2,JohannesKettunen1,2,RiittaLuoto3, VeikkoSalomaa2,ElisabethWide′n1* 1InstituteforMolecularMedicineFinlandFIMM,UniversityofHelsinki,Helsinki,Finland,2NationalInstituteforHealthandWelfare,Helsinki,Finland,3UKKInstitutefor HealthPromotion,Tampere,Finland Abstract Context:Pubertaltimingisunderstronggeneticcontrolanditsearlyonsetassociateswithseveraladversehealthoutcomes in adulthood, including obesity, type 2 diabetes and cardiovascular disease. Recent data indicate strong association betweenpubertaltimingandgeneticvariantsnearLIN28B,butitiscurrentlyunknownwhetherthegenecontributestothe associationbetweenpubertyandadultdisease. Objective:Toelucidatetheputativegeneticlinkbetweenearlypubertyandadultdiseaserisk,weexaminedtheassociation oftwogeneticvariantsnearLIN28BwithadultbodysizeandmetabolicprofilesinrandomlyascertainedadultFinnishmales andfemales. Methods:Twosinglenucleotidepolymorphisms(SNPs),rs7759938,theleadSNPpreviouslyassociatedwithpubertaltiming and height, and rs314279, previously also associated with menarcheal age but only partially correlated with rs7759938 (r2=0.30), were genotyped in 26,636 study subjects participating in the Finnish population survey FINRISK. Marker associationswithadultheight,weight,bodymassindex(BMI),hipandwaistcircumference,bloodglucose,seruminsulin andlipid/lipoproteinlevelsweredeterminedbylinearregressionanalyses. Results:Bothrs7759938andrs314279associatedwithadultheightinbothsexes(p=261026andp=0.001).Furthermore, rs314279 associated with increased weight in females (p=0.001). Conditioned analyses including both SNPs in the regression model verified that rs314279 independently associates with adult female weight, BMI and hip circumference (p,0.005).NeitherSNPassociatedwithglucose,lipid,orlipoproteinlevels. Conclusion: Genetic variants near the puberty-associated gene LIN28B associate with adult weight and body shape in female