Role of genetic polymorphism peroxisome proliferator-activated receptor-gamma2 Pro12Ala on ethnic susceptibility to diabetes in South-Asian and Caucasian subjects: Evidence for heterogeneity.
OBJECTIVE
To determine whether the peroxisome proliferator-activated receptor (PPAR)-gamma Pro12ala polymorphism modulates susceptibility to diabetes in South Asians.


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 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.


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.
Radha
Venkatesan
V
Department of Molecular Genetics, Madras Diabetes Research Foundation, Dr. Mohan's Diabetes Specialties Centre, No. 4, Conran Smith Road, Gopalapuram, Chennai-86, India. radhav@yahoo.com
Vimaleswaran
Karani S
KS
Babu
Hunsur Narayan S
HN
Abate
Nicola
N
Chandalia
Manisha
M
Satija
Pankaj
P
Grundy
Scott M
SM
Ghosh
Saurabh
S
Majumder
Partha P
PP
Deepa
Raj
R
Rao
Sathyanarayana M R
SM
Mohan
Viswanathan
V
D015502:Absorptiometry, Photon; D000328:Adult; D000368:Aged; D000409:Alanine; D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics; D017931:DNA Primers; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D047495:PPAR gamma / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011392:Proline; D012016:Reference Values; D044465:White People / Q000235:genetics
D017931:DNA Primers; D047495:PPAR gamma; D011392:Proline; D000409:Alanine