Prospective study on the components of metabolic syndrome and the incidence of Parkinson's disease

Sääksjärvi, Katri; Knekt, Paul; Männistö, Satu; Lyytinen, Jukka; Heliövaara, Markku

doi:10.1016/j.parkreldis.2015.07.017

Cited by 53 publications

(62 citation statements)

References 34 publications

(55 reference statements)

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“…Furthermore, weight loss that could occur during the early course of PD 29,30 might affect the risk estimation because this study was conducted with a relatively short follow-up period (median 6.4 years); therefore, the individuals who had already developed pathological changes in their body but were diagnosed with PD only after developing overt clinical signs later, might have been included in the initial population, even though we applied a 1-year lag period. Several prospective cohort studies reported the relationship between metabolic syndrome and the future risk of PD 10,31 . One nationwide cohort analysis showed that metabolic syndrome increased the risk of PD.…”

Section: Discussionmentioning

confidence: 99%

Serum gamma-glutamyltransferase activity and Parkinson’s disease risk in men and women

Yoo

Kim

Jung

et al. 2020

Sci Rep

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We evaluated serum gamma-glutamyltransferase (GGt) and the risk of parkinson's disease (pD). Using data from the National Health Insurance Service (NHIS) database, we constructed a cohort consisting of individuals aged above 40 years who underwent a health check-up in 2009. After excluding individuals with heavy alcohol consumption, hepatobiliary and pancreatic disorders, and a previous history of PD, each quartile group of baseline serum GGT levels was monitored for the development of PD for 7 years. Adjusted hazard ratios (HRs) for PD were estimated by Cox proportional hazard models adjusting for potential confounding variables. We additionally analyzed the possible interaction between GGT and obesity or metabolic syndrome. Among the 6,098,405 individuals who were included, PD developed in 20,895 individuals during the follow-up (0.34%, 9,512 men and 11,383 women). The top quartile of serum GGT (geometric means, 90.44 IU/L in men and 41.86 IU/L in women) was associated with a lower risk in men (adjusted HR = 0.72 (95% CI: 0.67-0.76)) and a higher risk in women (adjusted HR = 1.30 (95% CI: 1.23-1.37)) using the lower GGT quartiles as a reference. Obesity and metabolic syndrome increased PD risk in both sexes, and there was only a subadditive interaction between serum GGT and obesity in women.Gamma-glutamyltransferase (GGT) is mainly located in the membrane of hepatocytes and is a marker of various disease conditions affecting the liver and hepatobiliary system 1,2 . Recently, the serum level of GGT has also been reported to be associated with vascular diseases, including ischemic heart disease and stroke, as well as with metabolic syndrome and dementia 3-8 . As GGT catalyzes the transfer of glutamyl residue from glutathione to an amino acid, it could be a marker of the oxidative stress burden and the subsequent development of neurodegenerative disease 9 . To investigate the relationship between the serum GGT level and the risk of Parkinson's disease (PD), we analyzed longitudinal big cohort data from the National Health Insurance Service (NHIS) database. ResultsBasic characteristics. We finally included a total of 6,098,405 individuals in the analysis. Baseline characteristics were compared among men and women in different quartiles of serum GGT activity (Table 1). There were factors that were significantly associated with serum GGT levels, e.g., age, low income, BMI, current smoking, mild-to-moderate alcohol consumption, exercise, diabetes mellitus (DM), hypertension, dyslipidemia, CKD, and metabolic syndrome (p < 0.0001). We considered all of these possible confounding variables when evaluating the independent relationship between GGT and PD.Baseline serum GGT activities and their impact on PD risk. During the median follow-up of 6.4 years, new-onset PD developed in 20,895 participants (0.34%; 9,512 (0.33%) men and 11,383 (0.35%) women). The incidence of PD gradually decreased in men, while it increased in women as GGT activity increased ( Table 2). The highest quartile of the GGT group had HRs for PD of 0.67 ...

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Section: Discussionmentioning

confidence: 99%

Serum gamma-glutamyltransferase activity and Parkinson’s disease risk in men and women

Yoo

Kim

Jung

et al. 2020

Sci Rep

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“…39 Apart from the observed dysregulated levels of cholesterol (metabolites) and cholesterol-containing lipoproteins in PD patients, lower serum levels of triglycerides—which are highly enriched in VLDL particles—associate with an increased PD risk. 45, 46 …”

Section: Discussionmentioning

confidence: 99%

Integrated molecular landscape of Parkinson’s disease

Klemann

Martens

Sharma

et al. 2017

npj Parkinson's Disease

105

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Parkinson’s disease is caused by a complex interplay of genetic and environmental factors. Although a number of independent molecular pathways and processes have been associated with familial Parkinson’s disease, a common mechanism underlying especially sporadic Parkinson’s disease is still largely unknown. In order to gain further insight into the etiology of Parkinson’s disease, we here conducted genetic network and literature analyses to integrate the top-ranked findings from thirteen published genome-wide association studies of Parkinson’s disease (involving 13.094 cases and 47.148 controls) and other genes implicated in (familial) Parkinson’s disease, into a molecular interaction landscape. The molecular Parkinson’s disease landscape harbors four main biological processes—oxidative stress response, endosomal-lysosomal functioning, endoplasmic reticulum stress response, and immune response activation—that interact with each other and regulate dopaminergic neuron function and death, the pathological hallmark of Parkinson’s disease. Interestingly, lipids and lipoproteins are functionally involved in and influenced by all these processes, and affect dopaminergic neuron-specific signaling cascades. Furthermore, we validate the Parkinson’s disease -lipid relationship by genome-wide association studies data-based polygenic risk score analyses that indicate a shared genetic risk between lipid/lipoprotein traits and Parkinson’s disease. Taken together, our findings provide novel insights into the molecular pathways underlying the etiology of (sporadic) Parkinson’s disease and highlight a key role for lipids and lipoproteins in Parkinson’s disease pathogenesis, providing important clues for the development of disease-modifying treatments of Parkinson’s disease.

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“…Most researchers agreed that serum total cholesterol and LDL in PD are lower as compared to controls (15). Recent Finnish study concluded that elevated serum triglycerides predicted low PD incidence (16). -lesterol and triglycerides in our ET patients.…”

Section: Discussionmentioning

confidence: 58%