Human peroxisome proliferator-activated receptor 2 [PPAR 2] pro 12 Ala polymorphism: a possible association with risk of diabetic nephropathy in type 2 diabetes

ABSTRACT

Mutations of the nuclear receptors PPAR-gamma confer an extreme phenotype of partial lipodystrophy, early-onset severe insulin resistance, type 2 diabetes, dyslipidemia, hypertension, and hepatic steatosis. The association between the Pro 12 Ala polymorphism in PPAR-gamma and obesity, insulin sensitivity, and type 2 diabetes was studied. It appears that the Ala 12 allele confers modest protection against the onset of type 2 diabetes and is also associated with an increased BMI in overweight individuals. This study was conducted to investigate an association between Pro 12 Ala polymorphism and the incidence of diabetic nephropathy in obese patients with long-lasting type 2 diabetes. The study was carried on sixty patients with type 2 diabetes mellitus, they were divided to 2 groups, group 1 included 30 patients with diabetic nephropathy and group 2 include 30 patients without diabetic nephropathy. Thirty healthy subjects of matched age and sex were included as controls [group 3]. Pro 12 Ala polymorphism was statistically significant more frequent in the diabetic group without nephropathy [group 2] in comparison to diabetic patients with nephropathy [group 1] p<0.0001, and the control group [group 3], p<0.0001. but there was no significant difference between the diabetic nephropathy group [group 1] and control group [group 3]. PPAR gamma receptor polymorphism was positive in 7 patients [23.33%] and negative in 23 patients [76.67%] of the diabetic nephropathy group [group 1]. In the diabetic group without diabetic nephropathy, it was positive in 24 patients [80%], negative in 6 patients [20%]. On the other hand, patient with diabetic nephropathy [group 1] associated with hypertension [21 patients] were all negative regarding PPAR gamma Pro 12 Ala polymorphism. Whereas, those without hypertension only 2 out of 9 patient were negative and the remaining 7 cases were positive regarding polymorphism. There were no significant differences between the two diabetic groups of patients regarding BMI, lipid profile and duration of diabetes. There was also no association between PPAR polymorphism and duration of diabetes, BMI and any of the biochemical parameters measured. In conclusion, the presence of the Ala allele of the PPAR gamma Pro 12 Ala polymorphism seems to be associated with a decreased risk of diabetic nephropathy in patients with type 2 diabetes. This association needs to be confirmed in other patient populations. More basic studies will be required to uncover the molecular mechanisms underlying the association between PPAR gamma Pro 12 Ala polymorphism and diabetic nephropathy risk