Role of genetic polymorphism peroxisome proliferator-activated receptor-γ2 Pro12Ala on ethnic susceptibility to diabetes in South-Asian and Caucasian subjects

被引:94
作者
Radha, V
Vimaleswaran, KS
Babu, HNS
Abate, N
Chandalia, M
Satija, P
Grundy, SM
Ghosh, S
Majumder, PP
Deepa, R
Rao, SMR
Mohan, V
机构
[1] Madras Diabet Res Fdn, Dr Mohans Diabet Special Ctr, Madras, Tamil Nadu, India
[2] Indian Inst Sci, Jawaharlal Nehru Ctr Adv Sci Res, Dept Biochem, Bangalore 560012, Karnataka, India
[3] Univ Texas, SW Med Ctr, Ctr Human Nutr, Dept Internal Med, Dallas, TX 75235 USA
[4] Indian Stat Inst, Kolkata 700035, W Bengal, India
关键词
D O I
10.2337/dc05-1473
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVE - To determine whether the peroxisome proliferator-activated receptor (PPAR)-gamma Pro12ala polymorphism modulates susceptibility to diabetes in South Asians. RESEARCH DESIGN AND METHODS - 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. RESULTS - 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 mu U/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. CONCLUSIONS - 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.
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页码:1046 / 1051
页数:6
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