San Luciano Marta, Wang Cuiling, Ortega Roberto A, Giladi Nir, Marder Karen, Bressman Susan, Saunders-Pullman Rachel
Department of Neurology Mount Sinai Beth Israel Medical Center New York New York.
Department of Neurology University of California San Francisco San Francisco California.
Ann Clin Transl Neurol. 2017 Oct 19;4(11):801-810. doi: 10.1002/acn3.489. eCollection 2017 Nov.
To evaluate sex differences and the relative effect of G2019S mutations in Parkinson's disease (PD).
530 PD carriers and 759 noncarrier PD (idiopathic, IPD) evaluated as part of the Fox Foundation (MJFF) Consortium were included. All participants completed a study visit including information on clinical features, treatment, examination, and motor and nonmotor questionnaires. Clinical features were compared between men and women separately for IPD and PD; and features were compared between IPD and PD separately for men and women.
: men had higher levodopa equivalency dose (LED), worse activities of daily living and motoric severity but lower complications of therapy (UPDRS-IV). IPD women had higher olfaction and thermoregulatory scores and were more likely to report family history of PD. Among : Male predominance was not observed among G2019S cases. Women had worse UPDRS-IV but better olfaction. : men and women had better olfaction than IPD counterparts. men demonstrated lower motor and higher cognitive, RBD and thermoregulation scores than IPD men and women had greater UDPRS-IV and rates of dyskinesia.
There were clinical differences between sexes with a more severe phenotype in IPD men and more complications of therapy in women. The more severe male phenotype was moderated by , with men and women showing less diversity of phenotype. Our study supports that both genetics and sex drive phenotype, and thus trials in and IPD should consider gender stratification in design or analysis.
评估帕金森病（PD）中G2019S突变的性别差异及相对影响。
纳入作为福克斯基金会（MJFF）联盟一部分进行评估的530例携带G2019S突变的PD患者和759例非携带G2019S突变的特发性帕金森病（IPD）患者。所有参与者均完成了一次研究访视，包括临床特征、治疗、检查以及运动和非运动问卷等方面的信息。分别对IPD组和携带G2019S突变的PD组的男性和女性的临床特征进行比较；并分别对男性和女性的IPD组和携带G2019S突变的PD组的特征进行比较。
携带G2019S突变的男性患者左旋多巴等效剂量（LED）更高，日常生活活动能力和运动严重程度更差，但治疗并发症（统一帕金森病评定量表第四部分，UPDRS-IV）更低。IPD女性患者嗅觉和体温调节评分更高，且更有可能报告帕金森病家族史。在携带G2019S突变的PD患者中：未观察到男性占优势。女性的UPDRS-IV评分更差，但嗅觉更好。携带G2019S突变的PD患者：男性和女性的嗅觉均优于IPD患者。携带G2019S突变的男性患者运动评分更低，认知、快速眼动睡眠行为障碍（RBD）和体温调节评分更高，而携带G2019S突变的女性患者UDPRS-IV评分更高且异动症发生率更高。
性别之间存在临床差异，IPD男性患者的表型更严重，女性患者的治疗并发症更多。携带G2019S突变的PD患者减轻了男性更严重的表型，携带G2019S突变的男性和女性表型差异较小。我们的研究支持遗传因素和性别均驱动表型，因此在携带G2019S突变的PD患者和IPD患者中的试验在设计或分析时应考虑性别分层。
