Common polymorphisms of the peroxisome proliferator-activated receptor–γ (Pro12Ala) and peroxisome proliferator-activated receptor–γ coactivator–1 (Gly482Ser) and the response to pioglitazone in Chinese patients with type 2 diabetes mellitus
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Abstract
We investigated the effects of the common polymorphisms in the peroxisome proliferator-activated
receptor-gamma (PPAR-gamma; Pro12Ala) and in PPAR-gamma coactivator-1(PGC-1; Gly482Ser)
genes on the response to pioglitazone in Chinese with type 2 diabetes mellitus. A
total of 250 patients with type 2 diabetes mellitus were treated with pioglitazone
(30 mg/d) for 24 weeks without a change in previous medications. All patients were
genotyped for the PPAR-gamma Pro12Ala and PGC-1 Gly482Ser polymorphisms. The Ala12Ala
and Pro12Ala genotypes (26.0% vs 13.5%, P = .025) and Ala allele (15.6% vs 7.3%, P
= .008) were significantly more frequent in pioglitazone responders than in nonresponders.
The distribution of PGC-1 genotypes and alleles was not significantly different between
responders and nonresponders. The decrease in fasting glucose (50.4 +/- 52.2 vs 43.3
+/- 51.7 mg/dL, P < .001) and hemoglobin A(1c) (0.57% +/- 1.44% vs 0.35% +/- 1.10%,
P = .004) levels was significantly greater in subjects with the Ala12 carriers (Pro12Ala
and Ala12Ala) than in those without the allele (Pro12Pro). Baseline fasting glucose
and triglyceride levels were related to the response of pioglitazone. Only the PPAR-gamma
Pro12Ala polymorphism was found to be associated with the response of pioglitazone
by multiple logistic regression analysis. The PPAR-gamma Pro12Ala gene polymorphism
is associated with the response to pioglitazone in Chinese patients with type 2 diabetes
mellitus. These findings may be helpful for targeted treatment of diabetes by identifying
patients who are likely to respond to pioglitazone.
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