BACKGROUND: Several clinical studies report increased risk of diabetes mellitus with pharmacologic treatment for hypertension (HTN). HTN genes may modify glycemic response to antihypertensive treatment. METHOD: The current study examined the association of 24 single nucleotide polymorphisms (SNPs) in 11 HTN candidate genes with fasting glucose measured at 2, 4, and 6 years after treatment initiation. The study sample included participants free of diabetes at baseline in the Genetics of Hypertension Associated Treatment (GenHAT) study (N = 9309). GenHAT participants were randomized to receive treatment with a diuretic (chlorthalidone), calcium channel blocker (amlodipine), or angiotensin-converting enzyme (ACE) inhibitor (lisinopril). Mixed models for repeated measures were employed to test for gene and pharmacogenetic associations with fasting glucose during follow-up. RESULTS:Fasting glucose at year 2 increased on average 6.8, 4.8 and 3.0 mg/dl from baseline in the chlorthalidone, amlodipine and lisinopril groups, respectively. Carrying the I allele (rs1799752) of the ACE I/D polymorphism was associated with lower fasting glucose levels (P = 0.02). Additionally, an ACE promoter polymorphism (-262, rs4291) was associated with lower fasting glucose for the model AA/AT vs. TT, which remained significant after correction for multiple testing (P = 0.001). Finally, a SNP in the α-subunit of the amiloride-sensitive epithelial sodium channel (SCNN1A, rs2228576) modified the association of amlodipine vs. chlorthalidone treatment with fasting glucose (P < 0.001). CONCLUSION: Further examination of these genes and their relationships with cardiometabolic disease could foster development of pharmacogenetic guidelines aimed to prevent increases in fasting glucose during antihypertensive treatment.
RCT Entities:
BACKGROUND: Several clinical studies report increased risk of diabetes mellitus with pharmacologic treatment for hypertension (HTN). HTN genes may modify glycemic response to antihypertensive treatment. METHOD: The current study examined the association of 24 single nucleotide polymorphisms (SNPs) in 11 HTN candidate genes with fasting glucose measured at 2, 4, and 6 years after treatment initiation. The study sample included participants free of diabetes at baseline in the Genetics of Hypertension Associated Treatment (GenHAT) study (N = 9309). GenHAT participants were randomized to receive treatment with a diuretic (chlorthalidone), calcium channel blocker (amlodipine), or angiotensin-converting enzyme (ACE) inhibitor (lisinopril). Mixed models for repeated measures were employed to test for gene and pharmacogenetic associations with fasting glucose during follow-up. RESULTS:Fasting glucose at year 2 increased on average 6.8, 4.8 and 3.0 mg/dl from baseline in the chlorthalidone, amlodipine and lisinopril groups, respectively. Carrying the I allele (rs1799752) of the ACE I/D polymorphism was associated with lower fasting glucose levels (P = 0.02). Additionally, an ACE promoter polymorphism (-262, rs4291) was associated with lower fasting glucose for the model AA/AT vs. TT, which remained significant after correction for multiple testing (P = 0.001). Finally, a SNP in the α-subunit of the amiloride-sensitive epithelial sodium channel (SCNN1A, rs2228576) modified the association of amlodipine vs. chlorthalidone treatment with fasting glucose (P < 0.001). CONCLUSION: Further examination of these genes and their relationships with cardiometabolic disease could foster development of pharmacogenetic guidelines aimed to prevent increases in fasting glucose during antihypertensive treatment.
Authors: M Ohishi; H Rakugi; T Miki; T Katsuya; A Okamura; K Kamide; Y Nakata; S Takami; H Ikegami; Y Yanagitani; Y Tabuchi; Y Kumahara; J Higaki; T Ogihara Journal: Clin Exp Pharmacol Physiol Date: 2000-07 Impact factor: 2.557
Authors: James H Jackson; John Sobolski; Russ Krienke; Ken S Wong; Feride Frech-Tamas; Brian Nightengale Journal: J Am Board Fam Med Date: 2008 Nov-Dec Impact factor: 2.657
Authors: Irene G M van Valkengoed; Karien Stronks; Ines N Hahntow; Joost B L Hoekstra; Frits Holleman Journal: Diabetes Res Clin Pract Date: 2008-04-24 Impact factor: 5.602
Authors: A H Danser; M A Schalekamp; W A Bax; A M van den Brink; P R Saxena; G A Riegger; H Schunkert Journal: Circulation Date: 1995-09-15 Impact factor: 29.690
Authors: Jason H Karnes; Yan Gong; Michael A Pacanowski; Caitrin W McDonough; Meghan J Arwood; Taimour Y Langaee; Carl J Pepine; Julie A Johnson; Rhonda M Cooper-Dehoff Journal: Pharmacogenet Genomics Date: 2013-12 Impact factor: 2.089
Authors: Jose M de Miguel-Yanes; Bianca Porneala; Michael J Pencina; Caroline S Fox; Jose C Florez; David S Siscovick; Josée Dupuis; James B Meigs Journal: J Hypertens Date: 2013-05 Impact factor: 4.844
Authors: J H Karnes; C W McDonough; Y Gong; T T Vo; T Y Langaee; A B Chapman; J G Gums; A L Beitelshees; K R Bailey; J L Del-Aguila; E A Boerwinkle; C J Pepine; S T Turner; J A Johnson; R M Cooper-DeHoff Journal: Pharmacogenomics J Date: 2012-08-21 Impact factor: 3.550
Authors: A N Do; A I Lynch; S A Claas; E Boerwinkle; B R Davis; C E Ford; J H Eckfeldt; H K Tiwari; D K Arnett; M R Irvin Journal: J Hum Hypertens Date: 2016-01-21 Impact factor: 3.012