Association of common gene variants in glucokinase regulatory protein with cardiorenal disease: A systematic review and meta-analysis

Pomme I H G Simons, Nynke Simons, Coen D A Stehouwer, Casper G Schalkwijk, Nicolaas C Schaper and Martijn C G J Brouwers

PLOS ONE, 2018, vol. 13, issue 10, 1-14

Abstract: Background: Small-molecules that disrupt the binding between glucokinase and glucokinase regulatory protein (GKRP) in the liver represent a potential new class of glucose-lowering drugs. It will, however, take years before their effects on clinically relevant cardiovascular endpoints are known. The purpose of this study was to estimate the effects of these drugs on cardiorenal outcomes by studying variants in the GKRP gene (GCKR) that mimic glucokinase-GKRP disruptors. Methods: The MEDLINE and EMBASE databases were searched for studies reporting on the association between GCKR variants (rs1260326, rs780094, and rs780093) and coronary artery disease (CAD), estimated glomerular filtration rate (eGFR), and chronic kidney disease (CKD). Results: In total 5 CAD studies (n = 274,625 individuals), 7 eGFR studies (n = 195,195 individuals), and 4 CKD studies (n = 31,642 cases and n = 408,432 controls) were included. Meta-analysis revealed a significant association between GCKR variants and CAD (OR:1.02 per risk allele, 95%CI:1.00–1.04, p = 0.01). Sensitivity analyses showed that replacement of one large, influential CAD study by two other, partly overlapping studies resulted in similar point estimates, albeit less precise (OR:1.02; 95%CI:0.98–1.06 and OR: 1.02; 95%CI: 0.99–1.04). GCKR was associated with an improved eGFR (+0.49 ml/min, 95%CI:0.10–0.89, p = 0.01) and a trend towards protection from CKD (OR:0.98, 95%CI:0.95–1.01, p = 0.13). Conclusion: This study suggests that increased glucokinase-GKRP disruption has beneficial effects on eGFR, but these may be offset by a disadvantageous effect on coronary artery disease risk. Further studies are warranted to elucidate the mechanistic link between hepatic glucose metabolism and eGFR.

Date: 2018
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0206174 (text/html)
https://journals.plos.org/plosone/article/file?id= ... 06174&type=printable (application/pdf)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0206174

DOI: 10.1371/journal.pone.0206174

Access Statistics for this article

More articles in PLOS ONE from Public Library of Science
Bibliographic data for series maintained by plosone ().