Genetic Risk Factors and the Anti-Atherosclerotic Effect of Pioglitazone on Carotid Atherosclerosis of Subjects with Type 2 Diabetes —A Retrospective Study—

Abstract

Aim: Pioglitazone, an agonist of peroxisome proliferator-activated receptor , showed various antiatherosclerotic effects on type 2 diabetic patients. This retrospective study was done to ascertain which risk factor(s) associate with anti-atherosclerotic effects of pioglitazone.

Current clinical evidence on pioglitazone pharmacogenomics

“…TZDs were shown to improve lipid profiles, inflammation, coagulation, and endothelial cell function, and PIO was shown to significantly slow progression of carotid intima-media thickness (IMT) (Saitou et al, 2010). In contrast to ROSI, which was associated with an increased risk of MI, meta-analyses showed that PIO did not increase the risk of MI and might have a benefit of decreasing revascularization events (Nagajothi et al, 2008; Tannen et al, 2013).…”

Long-Term Effects of Pioglitazone on Carotid Atherosclerosis in Japanese Patients with Type 2 Diabetes without a Recent History of Macrovascular Morbidity

“…Furthermore, pioglitazone can modify systemic inflammatory and coagulation markers 8,9) . Recently, pioglitazone was found to modify the progression of carotid atherosclerosis induced by various genetic risk factors 28) . Taken together, the overall pattern of changes induced by pioglitazone suggests a general improvement in a number of different risk factors associated with atherosclerosis.…”

Pharmacogenomics and Pharmacogenetics of Thiazolidinediones: Role in Diabetes and Cardiovascular Risk Factors

“…A genetic study by Saitou et al . [79] has shown that the ameliorative potential of pioglitazone on diabetic aggravation of atherosclerosis is independent of the tested genotypes. Polymorphism (S447X) in the LPL gene influences the beneficial effects of pioglitazone on cardiovascular complications of diabetes mellitus [80].…”

“…Aimed to investigate the genetic impact in the atheroprotective effects of TZDs, Saitou et al . [79] analyzed 99 candidate SNPs and their possible associations with conventional vascular risk factors and the progression or regression of carotid atherosclerosis in diabetic patients treated with pioglitazone or only with diet. Among the analyzed genetic variants, the I/D polymorphism in the ACE gene and the C677T polymorphism in the MTHFR gene showed a significant association with changes in the values of averaged and maximum IMT, a subclinical markers of atherosclerosis, in both group of patients.…”

“…In particular, the group of patients carrying the ACE D-allele and treated with pioglitazone had lower increase in IMT than the group treated with diet alone (p = 0.01). In addition, pioglitazone exerts a protective effect attenuating the increase in IMT (p = 0.03) in patients carriers the 677T allele in the MTHFR gene which is generally associated to higher homocysteine level and progression of atherosclerosis [79]. These findings strongly suggest as TZDs may have a pleiotropic effects exerting their action through PPAR-γ at different molecular levels such as renin-angiotensin modulation.…”