Dataset Information

Serum Gamma-Glutamyl Transferase and Ferritin Synergistically Associated with the Rate of Chronic Kidney Disease.

ABSTRACT: The present study investigated the effects of GGT and SF on the risk of CKD. 1024 participants (436 men and 588 women) were divided into three groups according to GGT and SF levels: group 1 (both GGT and SF not in the fourth quartile), group 2 (only GGT or SF in the fourth quartile), and group 3 (both GGT and SF in the fourth quartile). The risks of CKD in different levels of GGT and SF and in groups 2-3 compared with group 1 were analyzed by multiple logistic regression. GGT or SF in the highest quartile was associated with increased risk of CKD. Such associations attenuated after adjustment for confounding factors. The incidences of CKD, especially albuminuria, increased across the three groups. Correspondingly, malondialdehyde (MDA) levels gradually increased from group 1 to group 3. The risks of CKD were higher in groups 2 and 3 than that in group 1. In group 3, the increased rate was independent of age, BMI, alcohol drinking, diabetes mellitus, hypertension, hypertriglyceridemia, and metabolic syndrome (odds ratios from 1.887 to 2.293, P < 0.05). In summary, this study suggested that GGT and SF synergistically influence the rate of CKD.

SUBMITTER: Chen T

PROVIDER: S-EPMC5474265 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Serum Gamma-Glutamyl Transferase and Ferritin Synergistically Associated with the Rate of Chronic Kidney Disease.

Chen Tao T Ren Yan Y Gao Yun Y Tian Haoming H

Disease markers 20170604

The present study investigated the effects of GGT and SF on the risk of CKD. 1024 participants (436 men and 588 women) were divided into three groups according to GGT and SF levels: group 1 (both GGT and SF not in the fourth quartile), group 2 (only GGT or SF in the fourth quartile), and group 3 (both GGT and SF in the fourth quartile). The risks of CKD in different levels of GGT and SF and in groups 2-3 compared with group 1 were analyzed by multiple logistic regression. GGT or SF in the highes ...[more]

PMID: 28659657

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Project description:Elevated Gamma-glutamyl transferase (GGT) levels are often suggestive of cholelithiasis, and previous studies have indicated that GGT is highly expressed in the urinary system. Therefore, we hypothesized that there may be an association between GGT levels and calculus of kidney (CK) incidence. To investigate this potential causal relationship, we employed Mendelian randomization (MR) analysis. Additionally, we analyzed the levels of other liver enzymes, including alanine transaminase (ALT) and alkaline phosphatase (ALP). The relationship between GGT levels and CK incidence was analyzed using two-sample Mendelian randomization. Summary Genome-Wide Association Studies data were utilized for this analysis. 33 single nucleotide polymorphisms known to be associated with GGT levels were employed as instrumental variables. We employed several MR methods including IVW (inverse variance weighting), MR-Egger, weighted median, weighted mode, and MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier). Furthermore, we conducted tests for horizontal multivariate validity, heterogeneity, and performed leave-one-out analysis to ensure the stability of the results. Overall, several MR methods yielded statistically significant results with a p-value < 0.05. The results from the IVW analysis yielded an odds ratio (OR) of 1.0062 with a 95% confidence interval (CI) of 1.0016-1.0109 (p = 0.0077). Additional MR methods provided supplementary results: MR-Egger (OR 1.0167, 95% CI 1.0070-1.0266, p = 0.0040); weighted median (OR 1.0058, 95% CI 1.0002-1.0115, p = 0.0423); and weighted mode (OR 1.0083, 95% CI 1.0020-1.0146, p- = 0.0188). Sensitivity analyses did not reveal heterogeneity or outliers. Although potential horizontal pleiotropy emerged, we speculate that this could be attributed to inadequate test efficacy. However, subsequent use of MR-PRESSO did not provide evidence of pleiotropy. Our analysis suggests a positive association between elevated GGT levels and CK incidence, indicating an increased risk of CK development. However, no causal relationship was observed between levels of ALP or ALT and CK incidence.

Project description:Background and aimsSerum levels of ?-glutamyl-transpeptidase(?-GT) were associated with liver disease severity and metabolic alterations, which in turn are able to affect hepatic damage. In patients with nonalcoholic fatty liver disease (NAFLD), genotype 1 chronic hepatitis C (G1CHC) and chronic hepatitis B (CHB), we assessed the link between liver fibrosis and ?-GT serum levels, and we evaluated if normal or high ?-GT serum levels affect the association between insulin resistance (IR) and severity of liver fibrosis.Methods843 consecutive patients with chronic liver disease (CLD)(193 NAFLD, 481 G1CHC, 169 CHB) were evaluated by liver biopsy (Kleiner and Scheuer scores) and clinical and metabolic measurements. IR was diagnosed if HOMA>3. A serum ?-GT concentration of >36 IU/L in females and >61 IU/L in males was considered the threshold value for identifying high levels of ?-GT.ResultsBy multivariate logistic regression analysis, abnormal ?-GT serum levels were independently linked to severe liver fibrosis in patients with NAFLD (OR2.711,CI1.120-6.564,p = 0.02), G1CHC (OR3.461,CI2.138-5.603,p<0.001) and CHB (OR2.778,CI1.042-7.414,p = 0.04), together with IR and liver necroinflammation, and with a negative predictive value>80%. Interestingly, among patients with high or normal ?-GT values, even if IR prevalence was significantly higher in patients with severe fibrosis compared to those without, IR remained significantly associated with severe fibrosis in patients with abnormal ?-GT values only (OR4.150,CI1.079-15.970,p = 0.03 for NAFLD; OR2.250,CI1.211-4.181,p = 0.01 for G1CHC; OR3.096,CI2.050-34.220,p = 0.01 for CHB).ConclusionsIn patients with CLD, IR is independently linked to liver fibrosis only in patients with abnormal ?-GT values, without differences according to liver disease etiology, and suggesting a role of ?-GT as a marker of metabolic-induced liver damage. These data could be useful for the clinical and pharmacologic management of patients with CLD.

Project description:Gamma-glutamyl transferase (GGT) is a biomarker of inflammation, and is known to be associated with stroke and atrial fibrillation. Venous thromboembolism (VT), a not uncommon thrombotic disorder, shares similar mechanisms with other thrombotic disorders including these stroke and atrial fibrillation. Given these associations, we intended to investigate the potential association between variability in GGT and VT. The study included data from the National Health Insurance Service-Health Screening Cohort, comprising 1,085,105 participants with health examinations 3 or more times from 2003 to 2008. Variability indexes were the coefficient of variation, standard deviation, and variability independent of the mean. The occurrence of venous thromboembolism (VT) was defined with more than one claim of the following ICD-10 codes: deep VT (I80.2-80.3), pulmonary thromboembolism (I26), intraabdominal venous thrombosis (I81, I82.2, I82.3), or other VT (I82.8, I82.9). To determine the relationship of quartiles of GGT with incident VT risk, Kaplan-Meier survival curve and logrank test were used. Cox's proportional hazard regression was used to investigate the risk of VT occurrence by GGT quartile (Q1-Q4). A total of 1,085,105 subjects were incorporated in the analysis, and the average follow-up was 12.4 years (interquartile range 12.2-12.6). VT occurred in 11,769 (1.08%) patients. The GGT level was measured 5,707,768 times in this stud. Multivariable analysis showed that GGT variability were positively associated with the occurrence of VT. Compared to the Q1, the Q4 showed an adjusted HR of 1.15 (95% CI 1.09-1.21, p < 0.001) when using coefficient of variation, 1.24 (95% CI 1.17-1.31, p < 0.001) when using standard deviation, and 1.10 (95% CI 1.05-1.16, p < 0.001) when using variability independent of the mean. Increased variability of GGT may be related to an increased risk of VT. Maintaining a stable GGT level would be beneficial in reducing the risk of VT.

Dataset Information

Serum Gamma-Glutamyl Transferase and Ferritin Synergistically Associated with the Rate of Chronic Kidney Disease.

Publications

Serum Gamma-Glutamyl Transferase and Ferritin Synergistically Associated with the Rate of Chronic Kidney Disease.

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