Effects of Pro12Ala polymorphism of peroxisome proliferator-activated receptor γ2 gene on rosiglitazone response in type 2 diabetes

Abstract

Patients with the Pro12Ala genotype in the PPARgamma2 gene had a better therapeutic response to rosiglitazone than did patients with the Pro12Pro genotype. The genetic variations in the PPARgamma2 gene can affect the response to rosiglitazone treatment in patients with type 2 diabetes mellitus.

LPIN1 genetic variation is associated with rosiglitazone response in type 2 diabetic patients

“…Multiple regression results showed that the rs10192566 genetic effect remained signifi cantly associated with rosiglitazone response (defi ned by a greater than 15% decrease in HbA1c levels after 12 weeks) after adjustment for age, gender, initial body weight gain, baseline FPG, and HOMA-IR [odds ratio (OR) 2.21, P = 0.013] ( Table 6). This genetic effect of LPIN1 became stronger when regression analysis included previously reported gene loci (adiponectin and PPAR-c, OR = 3.39, P = 0.004) [9,10].…”

“…Only lipin b increased with PPAR-c activator treatment [6], which is a possible mechanism of insulin-sensitizing action and increasing body weight in TZD treatment. We ex tended our previous studies [9,10] to investigate the association of rosiglitazone response to LPIN1 gene variations in 261 patients with T2DM. Similar to the results of previous studies, rs1163809, rs10192566, and rs2278513 were in nearly complete linkage disequilibrium [7].…”

“…However, the ex act molecular mechanism remains unknown and will need to be subject to further studies. Response was defi ned by a greater than 15% decrease in HbA1c levels after 12 weeks of rosiglitazone treatment (10). OR, odds ratio; CI, confi dence interval; FPG, fasting plasma glucose; HOMA-IR, homeostasis model analysis of insulin resistance.…”

“…Statistical analyses of triglyceride, HDL cholesterol, fasting insulin, and HOMA-IR levels were performed using log-transformed values for non-normally distributed data. Responders were defi ned by a greater than 15% decrease in HbA1c levels after 12 weeks according to our previous work [10]. P-values < 0.05 were considered signifi cant.…”

“…These studies implicate a role for LPIN1 genetic variation in glucose homeostasis and lipid metabolism. We have previously reported that genetic variations in adiponectin, PPAR-c2, and perilipin affect rosiglitazone response in patients with type 2 diabetes (T2DM) [9][10][11]. In this study, we ex tended our previous study cohort and evaluated the effects of LPIN1 polymorphisms on rosiglitazone response in T2DM.…”