Differences in Sex-Specific Frequency of Glucocerebrosidase Variant Carriers and Familial Parkinsonism.
Differences in Sex-Specific Frequency of Glucocerebrosidase Variant Carriers and Familial Parkinsonism.
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DOI：
10.1002/mds.29197
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发表时间：
2022-11
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虽然携带LRRK 2 G2019 S变异的男性和女性似乎同样可能患有帕金森病（PD），但GBA变异携带者的性别分布（包括限于GBA的特定变异严重程度）尚不清楚。此外，性别特异性遗传贡献PD没有已知的遗传变异是有争议的。更好地了解PD遗传贡献的性别差异，特别是GBA变异携带者PD（GBA PD）和LRRK 2-G2019 S变异携带者PD（LRRK 2 PD）的性别特异性频率。我们评估了性别特异性GBA PD发生率的差异，包括在德系犹太人PD队列中GBA变异严重程度、LRRK 2 PD和特发性PD的子集。此外，我们扩大了以前的工作评估帕金森氏症家族史的差异。特发性PD（267/420名男性，63.6%）（p<0.001）和总体GBA PD（64/107，59.8%）（p=0.042）更有可能是男性，而LRRK 2 PD（50/99，50.5%）和LRRK 2/GBA PD（5/10，50%）没有差异。然而，在GBA PD先证者中，重度变异携带者更可能是女性（15/19名女性，79.0%）（p=0.005），而轻度变异携带者（44/70名男性，62.9%）（p=0.039）和风险变异携带者（15/17名男性，88.2%）（p=0.001）更可能是男性。我们的研究表明，GBA PD总体上以男性为主，在GBA变异严重程度之间并不一致，严重的GBA变异携带者中以女性为主。因此，PD的研究和试验设计应考虑性别特异性差异，包括GBA变异严重程度。
While men and women with the LRRK2 G2019S variant appear to be equally likely to have Parkinson disease (PD), the sex-distribution among GBA variant carriers with PD, including limited to specific variant severities of GBA, is not well understood. Further, the sex-specific genetic contribution to PD without a known genetic variant is controversial. To better understand sex differences in genetic contribution to PD, especially sex-specific frequencies among GBA variant carriers with PD (GBA PD) and LRRK2-G2019S variant carriers with PD (LRRK2 PD). We assess differences in the sex-specific frequency in GBA PD, including in subsets of GBA variant severity, LRRK2 PD, and idiopathic PD in an Ashkenazi Jewish cohort with PD. Further, we expand prior work evaluating differences in family history of Parkinsonism. Both idiopathic PD (267/420 men, 63.6%) (p<0.001) and GBA PD overall (64/107, 59.8%) (p=0.042) were more likely to be men, while no difference was seen in LRRK2 PD (50/99, 50.5%) and LRRK2/GBA PD (5/10, 50%). However, among GBA PD probands, severe variant carriers were more likely to be women (15/19 women, 79.0%) (p=0.005), while mild variant carriers (44/70 men, 62.9%) (p=0.039) and risk-variant carriers (15/17 men, 88.2%) (p=0.001) were more likely to be men. Our study demonstrates that the male-sex predominance present in GBA PD overall was not consistent across GBA variant severities, and a female-sex predominance was present among severe GBA variant carriers. Thus, research and trial designs for PD should consider sex-specific differences, including across GBA variant severities.