Pacholczyk Marta, Ferenc Tomasz, Kowalski Jan, Adamczyk PrzemysÅaw, Chojnowski Jacek and Ponikowska Irena
Background: Angiotensinogen and its cleaved form - angiotensin II are important regulators of adipose tissue metabolism and they may affect adipogenesis. Aim: We studied the correlation between M235T and T174M polymorphisms of angiotensinogen (AGT) gene and morbid obesity and their association with Type 2 Diabetes Mellitus (T2DM). We also investigated the role of haplotypes formed by these polymorphisms in the risk for extreme obesity and obesity- associated T2DM.
Material and methods: The study included 335 morbidly obese patients (study groups) and 230 subjects without obesity (control group). The molecular analysis was performed using Polymerase Chain Reaction (PCR) and PCR-restriction fragment length polymorphism technique.
Results: Distribution of the genotype for AGT M235T polymorphism differed significantly between the controls and all extremely obese patients (p<0.05) and diabetic extremely obese patients (p<0.05). No significant differences were observed for AGT T174M polymorphism between the control and study groups (p>0.1). AGT gene polymorphic variants did not display any difference in clinical or metabolic parameters according to each genotype for either the control or the morbidly obese group. In univariate logistic regression analysis, the carriers for T235T and T174M (Hap2Hap3) had lower risk for extreme obesity (p<0.05). Homozygosity for both T235T and T174T (Hap2Hap2) was associated with decreased risk for extreme obesity and concomitant T2DM (p<0.05).
Conclusion: M235T but not T174M polymorphism of angiotensinogen (AGT) gene, may be linked with extreme obesity and T2DM in the investigated group of patients. On the basis of our results, we suggest that the risk of extreme obesity, irrespective of T2DM, was lower in Hap2Hap3 haplotype pair carriers. The Hap2Hap2 haplotype pair may be a significant protective factor for morbid obesity with T2DM and T2DM development in extreme obesity status (p<0.05).