Gender differences in prevalence of LRRK2-associated Parkinson disease: A meta-analysis of observational studies

Chen, Weiyao; Yan, Xuejing; Lv, Hong; Liu, Yang; He, Zhiwei; Luo, Xiaoguang

doi:10.1016/j.neulet.2019.134609

Cited by 21 publications

(17 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…70 The cumulative incidence of LRRK2 Arg1441Cys was found to be the least penetrant, with a median AAO of 71 years, whereas LRRK2 Asn1437His the most highly penetrant, with a median AAO of 46 years. 69 Additional studies found a "sex effect" in the prevalence of LRRK2-associated PD, [71][72][73][74] whereas others have reported similar PD penetrance in male and female patients carrying LRRK2 mutations. [75][76][77] As for idiopathic PD, the role of NSAIDs has been explored in LRRK2-associated PD, because LRRK2 is expressed in immune cells, such as microglia, and may be involved in inflammatory processes.…”

Section: Comorbiditiesmentioning

confidence: 99%

Effect Modification between Genes and Environment and Parkinson's Disease Risk

Periñán

Brolin

Bandrés‐Ciga

et al. 2022

Annals of Neurology

View full text Add to dashboard Cite

Parkinson's disease (PD) is a complex neurodegenerative condition in which genetic and environmental factors interact to contribute to its etiology. Remarkable progress has been made in deciphering disease etiology through genetic approaches, but there is limited data about how environmental and genetic factors interact to modify penetrance, risk, and disease severity. Here, we provide insights into environmental modifiers of PD, discussing precedents from other neurological and non-neurological conditions. Based on these examples, we outline genetic and environmental factors contributing to PD and review potential environmental modifiers of penetrance and clinical variability in monogenic and idiopathic PD. We also highlight the potential challenges and propose how future studies might tackle these important questions.

show abstract

Section: Comorbiditiesmentioning

confidence: 99%

Effect Modification between Genes and Environment and Parkinson's Disease Risk

Periñán

Brolin

Bandrés‐Ciga

et al. 2022

Annals of Neurology

View full text Add to dashboard Cite

show abstract

“…(which was not certified by peer review) PD cases in certain ethnic groups 60 . Differences in PD risk and presentation between men and women with LRRK2 G2019S mutations have been well characterized in the field [61][62][63] . Overall, women have a relatively higher incidence of having a LRRK2 G2019S mutation compared to men, and studies observed differences in presentation and medication dosages between men and women with LRRK2 mutation status 61,64 .…”

Section: Discussionmentioning

confidence: 99%

Association of Women-Specific Health Factors in the Severity of Parkinson’s Disease

Rao

Li²,

Lapin³

et al. 2022

Preprint

View full text Add to dashboard Cite

Background Parkinson′s disease (PD) is an age-related neurological disorder known for the observational differences in its risk, progression, and severity between men and women. While estrogen has been considered to be a protective factor in the development of PD, there is little known about the role that fluctuations in hormones and immune responses from sex-specific health experiences have in the disease′s development and severity. Objective We sought to identify women-specific health experiences associated with PD severity by developing and distributing a women-specific questionnaire across the United States. Design We created a questionnaire that addresses women′s specific experiences and their PD clinical history and deployed it through The Parkinson′s Foundation: PD Generations. To determine the association between women-specific health factors and PD severity, we constructed multivariable logistic regression models based on the MDS-UPDRS scale and the participants′ questionnaire responses, genetics, and clinical data. Results For our initial launch in November 2021, we had 304 complete responses from PD GENEration. Univariate and multivariate logistic modeling found significant associations between major depressive disorder, perinatal depression, natural childbirth, LRRK2 genotype, B12 deficiency, total hysterectomy and increased PD severity. Conclusions This study is the first nationally available questionnaire for women′s health and PD. It shifts the paradigm in understanding PD etiology and acknowledging how sex-specific experiences may contribute to PD severity. In addition, the work in this study sets the foundation for future research to investigate the reasons behind the sex differences in PD.

show abstract

“…In mouse, the SRY gene promotes catecholamine production by dopaminergic neurons of the substantia nigra [47], and rat models with repressed SRY expression show protection from experimentally induced PD [48]. A recent analysis shows an elevated prevalence of PD in females with the LRRK2 G2019S mutation [49]. Sexual dimorphism has been observed in the inflammatory response to traumatic brain injury in rodents [50,51], and there is some limited information on sex differences in eicosanoid biology [52].…”

Section: Discussionmentioning

confidence: 99%

Sex specific inflammatory profiles of cerebellar mitochondria are attenuated in Parkinson’s disease

Ingram

Shephard

Sarmad

et al. 2020

Aging

View full text Add to dashboard Cite

Response to inflammation is a key determinant in many diseases and their outcomes. Diseases that commonly affect older people are frequently associated with altered inflammatory processes. Neuroinflammation has been described in Parkinson's disease (PD) brain. PD is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta and at the sub-cellular level, mitochondrial dysfunction is a key feature. However, there is evidence that a different region of the brain, the cerebellum, is involved in the pathophysiology of PD. We report relative levels of 40 pro-and anti-inflammatory cytokines measured in PD and control cerebellar mitochondria. These data were obtained by screening cytokine antibody arrays. In parallel, we present concentrations of 29 oxylipins and 4 endocannabinoids measured in mitochondrial fractions isolated from post-mortem PD cerebellum with age and sex matched controls. Our oxylipin and endocannabinoid data were acquired via quantitation by LC-ESI-MS/MS. The separate sample sets both show there are clearly different inflammatory profiles between the sexes in control samples. Sex specific profiles were not maintained in cerebellar mitochondria isolated from PD brains.

show abstract

Gender differences in prevalence of LRRK2-associated Parkinson disease: A meta-analysis of observational studies

Cited by 21 publications

References 36 publications

Effect Modification between Genes and Environment and Parkinson's Disease Risk

Effect Modification between Genes and Environment and Parkinson's Disease Risk

Association of Women-Specific Health Factors in the Severity of Parkinson’s Disease

Sex specific inflammatory profiles of cerebellar mitochondria are attenuated in Parkinson’s disease

Contact Info

Product

Resources

About