Neurology：颅内动脉瘤家族史与早发破裂无关

左为颅内动脉瘤示意图；右为常见动脉瘤类型美国学者组织的一项国际多中心研究表明，有颅内动脉瘤（IA）家族史的患者发生IA破裂的年龄不一定早于其亲代。相关论文发表于《神经病学》杂志[Neurology2009,72（8）:695]。该研究入选429个家族，每个家族中至少有1例颅内动脉瘤破裂的患者。研究者对1600余名观察对象进行探访及评估（第一代与第二代家族成员的随访时间相似），并利用Cox比例风险回归模型及卡普兰-迈耶（Kaplan-Meier）曲线对两代家族成员的差异进行比较后发现，第二代家族成员发生IA破裂的平均年龄稍迟于第一代，且前者早期IA破裂率为后者的50%，但该比例随年龄增长逐渐趋近于第一代。上述研究结果有悖于多项既往研究结果，即第二代家族成员发生IA破裂的年龄早于第一代。究其原因主要在于既往研究对第二代家族成员的随访时间过短，而通过Kaplan-Meier曲线分析后，可得到不同结论。研究者认为，家族性IA并未呈现出遗传早现。遗传流行病学应着重对所有与IA破裂相关的基因变异（如单碱基对改变、缺失、插入等）进行检测，并对未显示遗传早现的其他变异加以关注。（生物谷Bioon.com）生物谷推荐原始出处：Neurology，2009;72:695-698，D.Woo，J.BroderickAgeatintracranialaneurysmruptureamonggenerationsFamilialIntracranialAneurysmStudyD.Woo,MD,MS,R.Hornung,PhD,L.Sauerbeck,RN,MS,R.Brown,MD,I.Meissner,MD,J.Huston,MD,T.Foroud,PhD,J.Broderick,MDFortheFIAInvestigators*FromtheDepartmentsofNeurology,EnvironmentalHealth,andCenterforEnvironmentalGenetics（D.W.,R.H.,L.S.,J.B.）,UniversityofCincinnati,OH;DepartmentofMedicalandMolecularGenetics（T.F.）,IndianaUniversitySchoolofMedicine,Indianapolis;andDepartmentsofNeurologyandNeuroradiology（R.B.,I.M.,J.H.）,MayoClinic,Rochester,MN.AddresscorrespondenceandreprintrequeststoDr.DanielWoo,DepartmentofNeurology,UniversityofCincinnatiCollegeofMedicine,231AlbertSabinWayML0525,Cincinnati,OHBackground:Previousstudieshavereportedintracranialaneurysm（IA）occurringatyoungagesinsubsequentgenerations.Thesestudiesdidnotcorrectfordurationoffollow-up.Second-generationmemberswhowouldhavetheirrupturedIAlateinlifemaynotbedetectedduetoshorterfollow-uptimethanthefirstgeneration.WeexaminedfamiliesinwhichrupturedIAoccurredintwoconsecutivegenerationsforthehypothesisthatthesecondgeneration（F1）wasmorelikelytohavearuptureatayoungeragethantheoldergeneration（F0）.Methods:TheFamilialIntracranialAneurysm（FIA）Studyisamulticenter,internationalstudyrecruitingfamiliesofrupturedandunrupturedIA.Allavailablefamilymembersareinterviewed.CoxproportionalhazardsregressionmodelsandKaplan-Meiercurveswereusedtoexaminedifferencesbygeneration.Results:AlthoughwefoundthattheF1generationwasmorelikelytohaveananeurysmruptureatayoungeragethantheF0generation,wefoundthatthiswaslargelybecauseofalackoffollow-uptimeintheF1generation.TheF1generationhad50%therupturerateofthepriorgeneration.WhenanalyzedbyKaplan-Meiercurves,wefoundatendencytohaveaslightlylaterrupturerateintheF1generationoncetimetofollow-upwasincludedintheanalysismodel.Conclusions:Familiesofrupturedintracranialaneurysm（IA）donotappeartodemonstrate"anticipation."OurfindingsuggeststhatgeneticepidemiologyofrupturedIAshouldexaminealltypesofvariationssuchassinglebase-pairchanges,deletions,insertions,andothervariationsthatdonotdemonstrateanticipation.

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