PPARγ2基因Pro12Ala多态性与罗格列酮治疗2型糖尿病疗效的关系

Relationship of Pro12Ala polymorphism of peroxisome proliferator activated receptor γ2(PPARγ2) gene on the therapeutic efficacy of rosiglitazone in the treatment of type 2 diabetes patients

目的观察PPARγ2基因Pro12Ala多态性与罗格列酮(RGZ)治疗2型糖尿病的疗效、血浆内脏脂肪素(visfatin)及瘦素(leptin)水平变化的关系。方法选择218例哈尔滨地区非血缘关系的T2DM患者,使用PCR-RFLP方法检测PPARγ2基因Pro12Ala多态性。应用RGZ(4 mg/d)治疗12周,分别测定治疗前后visfatin、leptin和相关临床指标,并计算胰岛素抵抗指数(HOMA-IR)。结果A等位基因频率为4.4%,其中PP型199例,PA型19例,未发现AA型。RGZ治疗后,PA型FPG、HbA1C较PP型明显下降(P<0.05),PA型HOMA-IR下降更显著(P<0.01);PA型和PP型治疗前后visfatin、leptin水平均明显下降(P<0.01)。结论PPARγ2基因为PA型者对RGZ的治疗反应优于PP型者。PPARγ2基因Pro12Ala多态性可能影响RGZ对T2DM患者的治疗效果。RGZ治疗效果可能与visfatin、leptin水平下降密切相关。

Objective To investigate the effects of the Pro12Ala polymorphism of PPARγ2 gene on the therapeutic efficacy of rosiglitazone（RGZ） in patients newly diagnosed type 2 diabetes（T2DM） and to explore the influence to the level of plasma visfatin,leptin and the relationship of Pro12Ala polymorphism of PPARγ2 gene.Methods Totally unrelated 218 T2DM patients in Harbin district were treated with RGZ（4 mg/day） for 12 weeks without withdrawing the previous medications.All patients were genotyped for the Pro12Ala polymorphism of PPARγ2 gene by PCR-RFLP and the levels of plasma vifatin,leptin and other clinical parameters were determined,the insulin resistance index（HOMA-IR） was calculated.Results The Ala12 allele frequency was 4.4%.Of the 218 patients,199 had the PP genotype and 19 had the PA genotype.The AA genotype was not observed.After RGZ treatment,the levels of fasting serum glucose（FPG） and glycohemoglobin（HbA1C） in the PA genotype decreased ]compared with the PP genotype（P〈0.05）.Moreover,the decrease in HOMA-IR level was significantly greater in the PA genotype than that in the PP genotype（P〈0.01）.The levels of plasma vifatin and leptin significantly decreased in post-RGZ treated PA gemotype and PP genotype patients compared to pre-RGZ treated patients（P〈0.01）.Conclusion T2DM patients with PA genotype in the PPARγ2 gene have a better therapeutic response to RGZ than patients with PP genotype.The Pro12Ala polymorphism of PPARγ2 gene may influence therapeutic response of RGZ to T2DM patients.The therapeutic efficacy to RGZ may be closely associated with decrease of plasma visfatin and leptin level.