Schäffler A, Barth N, Schmitz G, Zietz B, Palitzsch K D, Schölmerich J
Department of Internal Medicine I, University of Regensburg, Germany.
Endocrine. 2001 Apr;14(3):369-73. doi: 10.1385/endo:14:3:369.
Peroxisome proliferation-activated receptor-gamma2 (PPARgamma2) is exclusively expressed in adipose tissue and belongs to the transcriptional regulators of adipocyte differentiation. Recently, two missense single-point mutations have been described in the PPARgamma2 gene: Pro12Ala and Pro115Gln. It was our aim to determine the frequency of these polymorphisms in a Caucasian cohort and to investigate their possible role in the pathogenesis of obesity, type 2 diabetes, and related metabolic disorders. The genotypes of 359 subjects (149 males, 210 females) with varying degrees of obesity and with or without type 2 diabetes were determined. Subsequent to genomic polymerase chain reaction amplification, the HpaII restriction fragment length polymorphism (RFLP) analysis and the HindII RFLP analysis were used for genotyping the Pro12Ala and Pro115Gln polymorphism, respectively. For the Pro115Gln polymorphism, all 359 subjects showed wild-type sequence, emphasizing the very rare occurrence of the mutated allele. For the Pro12Ala polymorphism, 276 subjects (76.9%) were homozygous for the wild-type allele, 80 (22.3%) were heterozygous, and only 3 (0.8%) were homozygous for the mutated allele. Genotype frequency was calculated to be 0.88 for the wild-type allele and 0.012 for the mutated allele. No significant differences were found in age; gender; body mass index; total cholesterol; low-density, high-density, and very low density lipoproteins; triglycerides; Lp(a); uric acid; and diabetes manifestation by comparing the different genotypes. Therefore, a major role of these polymorphisms in the pathogenesis of obesity and diabetes can be excluded.
过氧化物酶体增殖物激活受体γ2（PPARγ2）仅在脂肪组织中表达，属于脂肪细胞分化的转录调节因子。最近，在PPARγ2基因中发现了两个错义单点突变：Pro12Ala和Pro115Gln。我们的目的是确定这些多态性在白种人队列中的频率，并研究它们在肥胖症、2型糖尿病及相关代谢紊乱发病机制中的可能作用。我们确定了359名不同程度肥胖且患有或未患有2型糖尿病的受试者（149名男性，210名女性）的基因型。在进行基因组聚合酶链反应扩增后，分别使用HpaII限制性片段长度多态性（RFLP）分析和HindII RFLP分析对Pro12Ala和Pro115Gln多态性进行基因分型。对于Pro115Gln多态性，所有359名受试者均显示野生型序列，这表明突变等位基因的出现非常罕见。对于Pro12Ala多态性，276名受试者（76.9%）为野生型等位基因纯合子，80名（22.3%）为杂合子，只有3名（0.8%）为突变等位基因纯合子。野生型等位基因的基因型频率计算为0.88，突变等位基因的基因型频率为0.012。通过比较不同基因型，在年龄、性别、体重指数、总胆固醇、低密度脂蛋白、高密度脂蛋白和极低密度脂蛋白、甘油三酯、Lp(a)、尿酸以及糖尿病表现方面未发现显著差异。因此，可以排除这些多态性在肥胖症和糖尿病发病机制中的主要作用。
