Potential Causal Association between Elevated Gamma-Glutamyl Transferase Level and Stroke: A Two-Sample Mendelian Randomization Study

Abstract

Researchers have suggested a potential relationship between gamma-glutamyl transferase (GGT) level and stroke. We investigated a potential causal relationship between GGT level as exposures and stroke and stroke subtypes (cardioembolic, small vessel, and large artery) in a European population. We performed a two-sample Mendelian randomization (MR) study using the genome-wide association study (GWAS) data from the UK Biobank as the exposure set. For the outcome set, we used stroke in the GWAS data from the GIGASTROKE Consortium. We considered alcohol consumption, atrial fibrillation, and body mass index as confounders. We used PhenoScanner searches for removal of SNPs and multivariable MR analysis for assessing confounders. We observed significant causal associations between GGT level and stroke (odds ratio [OR] = 1.23, 95% CI = [1.05–1.44], and p = 0.012 with IVW; OR = 1.19, 95% CI= [1.02–1.39], and p = 0.031 with MR-PRESSO). These results were consistent after removing SNPs related to confounding factors. Similarly, in multivariable MR, GGT was associated with stroke after adjusting for confounding factors (OR = 1.30, 95% CI 1.07–1.60), p = 0.010). Because GGT level has a causal relationship with stroke, researchers should test its significance as a potential risk factor for stroke. Additional research is required to validate these results.

Medical Ozone: A Redox Regulator with Selectivity for Rheumatoid Arthritis Patients

“…GGT is regulated by medical ozone in patients with RA and OA, and is a marker of the patient’s response to treatment [ 29 , 30 ]; it is activated by oxidants and is associated with Nrf2-mediated signaling mechanisms [ 31 ]. It has been considered as a marker of oxidative stress as well as a risk indicator for diseases with high morbidity and mortality (pancreatic cancer [ 32 ], stroke [ 33 ], osteoporotic fractures [ 34 ], etc.).…”

Bidirectional Mendelian randomization study shows causal relationship between high- altitude adaptation and liver diseases

“…Here we used data from the largest known GWASs to assess the casual effect between HAA and liver diseases/traits. Clinically, serum GGT has been commonly used as an biomarker of hepatobiliary diseases, and increased GGT levels accompanied by elevated free radical and a risk of imbalanced glutathione (GSH) (27). GGT locates on the cell surface and hydrolyzes the γ-glutamyl bonds of extracellular reduction and oxidation of GSH(28).…”

“…In addition, GGT plays a crucial role in antioxidant, detoxi cation and in ammation (29). Several recent studies showed the causal relationships of type 2 diabetes (30), stroke (27), calculus of kidney (31) on GGT. At present, there are few reports on the relationship between HAA and GGT.…”