Use of a Mendelian randomization approach to assess the causal relation of gamma-Glutamyltransferase with blood pressure and serum insulin levels.
Elevated levels of γ-glutamyltransferase (GGT) have been associated with elevated blood pressure (BP) and diabetes. However, the causality of these relations has not been addressed. The authors performed a cross-sectional analysis (2003-2006) among 4,360 participants from the population-based Cohorte Lausannoise (CoLaus) Study (Lausanne, Switzerland). The rs2017869 variant of the γ-glutamyltransferase 1 (GGT1) gene, which explained 1.6% of the variance in GGT levels, was used as an instrument for Mendelian randomization (MR). Sex-specific GGT quartiles were strongly associated with both systolic and diastolic BP (all P's < 0.0001). After multivariable adjustment, these relations were attenuated but remained significant. Using MR, the authors observed no positive association of GGT with BP (systolic: β -5.68, 95% confidence interval (CI): -11.51, 0.16 (P = 0.06); diastolic: β = -2.24, 95% CI: -5.98, 1.49 (P = 0.24)). The association of GGT with insulin was also attenuated after multivariable adjustment but persisted in the fully adjusted model (β = 0.07, 95% CI: 0.04, 0.09; P < 0.0001). Using MR, the authors also observed a positive association of GGT with insulin (β = 0.19, 95% CI: 0.01, 0.37; P = 0.04). In conclusion, the authors found evidence for a direct causal relation of GGT with fasting insulin but not with BP.
Department of Medicine, University Hospital Basel, Basel, Switzerland.
David
D
Conen
Peter
P
Vollenweider
Valentin
V
Rousson
Pedro
P
Marques-Vidal
Fred
F
Paccaud
Gérard
G
Waeber
Murielle
M
Bochud
D000328:Adult; D000368:Aged; D015984:Causality; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics; D005260:Female; D006801:Humans; D006973:Hypertension / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D057182:Mendelian Randomization Analysis; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D005723:gamma-Glutamyltransferase / Q000235:genetics* / Q000378:metabolism
D007328:Insulin; D005723:gamma-Glutamyltransferase