Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 (PPARgamma-2) gene is associated with greater insulin sensitivity and decreased risk of type 2 diabetes in an Iranian population.
BACKGROUND
The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 (PPARgamma-2) gene has been variably associated with insulin resistance, obesity and type 2 diabetes in several populations. However, this association has not been studied in Iranian subjects and we hypothesized that this variation might be associated with insulin resistance, type 2 diabetes and related metabolic traits in this population.


METHODS
The Pro12Ala genotypes were determined by PCR-restriction fragment length polymorphism in 696 unrelated subjects including 412 non-diabetic controls and 284 type 2 diabetic patients.


RESULTS
The frequency of the Ala allele was 9.4% and 5.9% in controls and type 2 diabetic subjects, respectively [adjusted odds ratio (OR) 0.457, p=0.005]. The Ala allele did not show a significant effect on anthropometric and biochemical parameters in the type 2 diabetic group, whereas in non-diabetic subjects, carriers of the Ala allele had significantly lower fasting insulin (p=0.007) and homeostasis model assessment of insulin resistance (HOMA-IR) (p=0.009) levels compared to Pro/Pro subjects. Multivariate logistic regression analysis showed that Pro12Ala polymorphism was an independent determinant of type 2 diabetes in this population.


CONCLUSIONS
Our results for a sample of Iranian type 2 diabetes cases and controls provide evidence that the Pro/Ala genotype of the PPARgamma-2 gene is associated with insulin sensitivity and may also have protective role against type 2 diabetes.
Meshkani
Reza
R
Endocrinology and Metabolism Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. meshk2000@yahoo.com
Taghikhani
Mohammad
M
Larijani
Bagher
B
Bahrami
Yadollah
Y
Khatami
Shohreh
S
Khoshbin
Ehteram
E
Ghaemi
Amir
A
Sadeghi
Sedigheh
S
Mirkhani
Fatemeh
F
Molapour
Azam
A
Adeli
Khosrow
K
D000409:Alanine / Q000235:genetics*; D001483:Base Sequence; D017931:DNA Primers; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D007492:Iran; D047495:PPAR gamma / Q000235:genetics*; D011110:Polymorphism, Genetic; D011392:Proline / Q000235:genetics*
D017931:DNA Primers; D047495:PPAR gamma; D011392:Proline; D000409:Alanine