PPARGC1A 基因多态性与亚洲印度人群糖尿病肾病的相关性研究（CURES-41）。

Association of the PPARGC1A gene polymorphism with diabetic nephropathy in an Asian Indian population (CURES-41).

机构信息

Madras Diabetes Research Foundation, and Dr. Mohan's Diabetes Specialities Centre, WHO Collaborating Centre for Noncommunicable Diseases Prevention Control, Gopalapuram, Chennai, India.

出版信息

Metab Syndr Relat Disord. 2010 Apr;8(2):119-26. doi: 10.1089/met.2009.0040.

DOI:10.1089/met.2009.0040

PMID:19900151

Abstract

BACKGROUND

The aim of this study was to evaluate the association of polymorphisms of the peroxisome proliferator-activated receptor gamma (PPARG) gene and peroxisome proliferators-activated receptor gamma co-activator 1 alpha (PPARGC1A) gene with diabetic nephropathy (DN) in Asian Indians.

METHODS

Six common polymorphisms, 3 of the PPARG gene [-1279G/A, Pro12Ala, and His478His (C/T)] and 3 of the PPARGC1A gene (Thr394Thr, Gly482Ser, and +A2962G) were studied in 571 normal glucose-tolerant (NGT) subjects, 255 type 2 diabetic (T2D) subjects without nephropathy, and 141 DN subjects. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing. Logistic regression analysis was performed to assess the covariables associated with DN.

RESULTS

Among the 6 polymorphisms examined, only the Gly482Ser of the PPARGC1A gene was significantly associated with DN. The genotype frequency of Ser/Ser genotype of the PPARGC1A gene was 8.8% (50/571) in NGT subjects, 7.8% (20/255) in T2D subjects, and 29.8% (42/141) in DN subjects. The odds ratios (ORs) for DN for the susceptible Gly/Ser and Ser/Ser genotype after adjusting for age, sex, body mass index, and duration of diabetes were 2.14 [95% confidence interval (CI), 1.23-3.72; P = 0.007] and 8.01 (95% CI, 3.89-16.47; P < 0.001), respectively. The unadjusted OR for DN for the XA genotype of the Thr394Thr polymorphism was 1.87 (95% CI, 1.20-2.92; P = 0.006) compared to T2D subjects. However, the significance was lost (P = 0.061) when adjusted for age, sex, BMI, and duration of diabetes. The +A2962G of PPARGC1A and the 3 polymorphisms of PPARG were not associated with DN.

CONCLUSION

The Gly482Ser polymorphism of the PPARGC1A gene is associated with DN in Asian Indians.

摘要

背景

本研究旨在评估过氧化物酶体增殖物激活受体γ（PPARG）基因和过氧化物酶体增殖物激活受体γ共激活因子 1α（PPARGC1A）基因多态性与亚洲印第安人糖尿病肾病（DN）的相关性。

方法

在 571 名糖耐量正常（NGT）受试者、255 名无肾病的 2 型糖尿病（T2D）受试者和 141 名 DN 受试者中研究了 6 个常见的多态性，即 3 个 PPARG 基因[-1279G/A、Pro12Ala 和 His478His（C/T）]和 3 个 PPARGC1A 基因（Thr394Thr、Gly482Ser 和 +A2962G）。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）和直接测序确定基因型。采用 logistic 回归分析评估与 DN 相关的协变量。

结果

在所检查的 6 个多态性中，只有 PPARGC1A 基因的 Gly482Ser 与 DN 显著相关。在 NGT 受试者中，PPARGC1A 基因 Ser/Ser 基因型的基因频率为 8.8%（50/571），T2D 受试者为 7.8%（20/255），DN 受试者为 29.8%（42/141）。在调整年龄、性别、体重指数和糖尿病病程后，易感 Gly/Ser 和 Ser/Ser 基因型的 DN 比值比（OR）分别为 2.14（95%可信区间，1.23-3.72；P=0.007）和 8.01（95%可信区间，3.89-16.47；P<0.001）。与 T2D 受试者相比，Thr394Thr 多态性的 XA 基因型的 DN 未调整 OR 为 1.87（95%可信区间，1.20-2.92；P=0.006）。然而，在调整年龄、性别、BMI 和糖尿病病程后，其意义丧失（P=0.061）。PPARGC1A 的+A2962G 和 PPARG 的 3 个多态性与 DN 无关。