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Effects of Pro12Ala polymorphism of peroxisome proliferator‐activated receptor γ2 gene on rosiglitazone response in type 2 diabetes
Author(s) -
Kang Eun Seok,
Park So Young,
Kim Hyeong Jin,
Kim Chul Sik,
Ahn Chul Woo,
Cha Bong Soo,
Lim Sung Kil,
Nam Chung Mo,
Lee Hyun Chul
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.04.013
Subject(s) - rosiglitazone , genotype , medicine , endocrinology , allele , peroxisome proliferator activated receptor , type 2 diabetes , diabetes mellitus , type 2 diabetes mellitus , polymorphism (computer science) , biology , receptor , gene , genetics
Objective The aim of this study was to examine the effects of the Pro12Ala polymorphism of the peroxisome proliferator‐activated receptor (PPAR) γ2 gene on the response to rosiglitazone in patients with type 2 diabetes mellitus. Methods A total of 198 patients with type 2 diabetes mellitus were treated with rosiglitazone (4 mg/d) for 12 weeks without a change in previous medications. All patients were genotyped for the PPARγ2 Pro12Ala polymorphism. Results The Ala12 allele frequency was 0.04. Of the 198 patients, 183 had the Pro12Pro genotype and 15 had the Pro12Ala genotype. The Ala12Ala genotype was not observed. The decrease in fasting plasma glucose level was significantly greater in subjects with the Ala12 allele than in those without the allele (50.6 ± 27.8 mg/dL versus 24.3 ± 41.9 mg/dL, P = .026). In addition, the decrease in hemoglobin A 1c level was significantly greater in subjects with the Ala12 allele than in those without the allele (1.41% ± 1.47% versus 0.57% ± 1.16%, P = .015). There was a significant difference in the response rate to rosiglitazone treatment between the Pro12Pro group and the Pro12Ala variant group (43.72% versus 86.67%, P = .002). Conclusion Patients with the Pro12Ala genotype in the PPARγ2 gene had a better therapeutic response to rosiglitazone than did patients with the Pro12Pro genotype. The genetic variations in the PPARγ2 gene can affect the response to rosiglitazone treatment in patients with type 2 diabetes mellitus. Clinical Pharmacology & Therapeutics (2005) 78 , 202–208; doi: 10.1016/j.clpt.2005.04.013