Radha Venkatesan, Vimaleswaran Karani S, Babu Hunsur Narayan S, Abate Nicola, Chandalia Manisha, Satija Pankaj, Grundy Scott M, Ghosh Saurabh, Majumder Partha P, Deepa Raj, Rao Sathyanarayana M R, Mohan Viswanathan
Department of Molecular Genetics, Madras Diabetes Research Foundation, Dr. Mohan's Diabetes Specialties Centre, No. 4, Conran Smith Road, Gopalapuram, Chennai-86, India.
Diabetes Care. 2006 May;29(5):1046-51. doi: 10.2337/diacare.2951046.
To determine whether the peroxisome proliferator-activated receptor (PPAR)-gamma Pro12ala polymorphism modulates susceptibility to diabetes in South Asians.
South Asians (n = 697) and Caucasians (n = 457) living in Dallas/Forth Worth, Texas, and South Asians living in Chennai, India (n = 1,619), were enrolled for this study. PPAR-gamma Pro12Ala was determined using restriction fragment-length polymorphism. Insulin responsiveness to an oral glucose tolerance test (OGTT) was measured in nondiabetic subjects.
The Caucasian diabetic subjects had significantly lower prevalence of PPAR-gamma 12Ala when compared with the Caucasian nondiabetic subjects (20 vs. 9%, P = 0.006). However, there were no significant differences between diabetic and nondiabetic subjects with reference to the Pro12Ala polymorphism among the South Asians living in Dallas (20 vs. 23%) and in India (19 vs. 19.3%). Although Caucasians carrying PPAR-gamma Pro12Ala had lower plasma insulin levels at 2 h of OGTT than the wild-type (Pro/Pro) carriers (76 +/- 68 and 54 +/- 33 microU/ml, respectively, P = 0.01), no differences in either fasting or 2-h plasma insulin concentrations were found between South Asians carrying the PPAR-gamma Pro12Ala polymorphism and those with the wild-type genotype at either Chennai or Dallas.
Although further replication studies are necessary to test the validity of the described genotype-phenotype relationship, our study supports the hypothesis that the PPAR-gamma Pro12Ala polymorphism is protective against diabetes in Caucasians but not in South Asians.
确定过氧化物酶体增殖物激活受体（PPAR）-γ Pro12ala多态性是否调节南亚人患糖尿病的易感性。
本研究纳入了居住在得克萨斯州达拉斯/沃思堡的南亚人（n = 697）和高加索人（n = 457），以及居住在印度金奈的南亚人（n = 1619）。使用限制性片段长度多态性测定PPAR-γ Pro12Ala。在非糖尿病受试者中测量口服葡萄糖耐量试验（OGTT）的胰岛素反应性。
与高加索非糖尿病受试者相比，高加索糖尿病受试者中PPAR-γ 12Ala的患病率显著更低（20%对9%，P = 0.006）。然而，在居住在达拉斯的南亚人（20%对23%）和印度的南亚人（19%对19.3%）中，糖尿病和非糖尿病受试者之间在Pro12Ala多态性方面没有显著差异。尽管携带PPAR-γ Pro12Ala的高加索人在OGTT 2小时时的血浆胰岛素水平低于野生型（Pro/Pro）携带者（分别为76±68和54±33微单位/毫升，P = 0.01），但在金奈奈或达拉斯携带PPAR-γ Pro12Ala多态性的南亚人与野生型基因型的南亚人之间，空腹或2小时血浆胰岛素浓度均无差异。
尽管需要进一步的重复研究来检验所描述的基因型-表型关系的有效性，但我们的研究支持以下假设，即PPAR-γ Pro12Ala多态性对高加索人患糖尿病有保护作用，而对南亚人则没有。
