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

Abstract

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 ...

Association Between Gamma-Glutamyl Transferase and Mild Cognitive Impairment in Chinese Women

“…Our study found an association between higher GGT and higher risk of cognitive impairment in the female population, which is consistent with previous studies in the male population (Kunutsor and Laukkanen, 2016 ). A study of GGT and Parkinson's disease is also consistent with our finding, that GGT may contribute to neurodegenerative disease in the female population (Yoo et al, 2020 ). However, contrary to our findings, a genetic study found no clear link between GGT and cognitive function (Kunutsor et al, 2018 ), possibly because that study did not include a subgroup analysis based on sex, which is essential because of the finding from previous study that estrogen may affect GGT activity in the body (Zarida et al, 1994 ).…”

“…We also asked them about their menstrual history to see if they had gone through menopause and their age at menopause. According to self-reported information, alcohol consumption was classified as heavy drinker (alcohol consumption ≥30 g/day), mild-moderate drinker (alcohol consumption <30 g/day) or abstainer (alcohol consumption = 0 g/day) (Yoo et al, 2020 ), and smoking status was classified as non-smoker or having quit more than 1 year ago or current smoker or having quit <1 year ago. BMI was defined based on the measured height and weight and calculated as weight (kg)/height (m 2 ).…”

Early Biomarkers of Neurodegenerative and Neurovascular Disorders in Diabetes

“…Last but not least in importance, GGT levels seem to affect the risk of stroke. The positive relationship between GGT concentrations and stroke were presented in a few independent studies [ 47 , 104 ]. Furthermore, a meta-analysis including 5707 stroke cases among 926,497 participants in 10 prospective studies stated that GGT level is an independent stroke risk factor [ 47 ].…”

“…GGT is a key player in glutathione metabolism, which is an essential cellular antioxidant [ 38 ]. GGT is a commonly used diagnostic test to assess liver function [ 104 ]. Yet, its role may be underestimated in pathologies of other systems, including diabetes and neurodegenerative diseases [ 39 ].…”

Effect of Metabolic Syndrome on Parkinson’s Disease: A Systematic Review

“…This study included six cohort studies (6,7,9,(15)(16)(17), four cross-sectional studies (18)(19)(20)(21), and one case-control study (22). The locations of the included studies (N=11) were as follows: three studies, South Korea (6,7,15); two studies, the United States of America (19,20); one study, Israel (18); one study, South Africa (22); one study, China (16); one study, Canada (17); one study, Italy (21); and one study, Finland (9) (Table 1).…”