Journal of School of Public Health and

Background and Aim: Type 2 diabetes mellitus is a heterogeneous disorder resulting from a combination of genetic and environmental factors which contribute to pathogenesis by influencing beta cell function and tissue insulin sensitivity. Protein tyrosine phosphatase 1B (PTP1B)" efficiently dephosphorylates the insulin receptor and attenuates insulin signaling. Recently, a 1484insG variant of the PTP1B gene was linked to increased risk of the metabolic syndrome in an Italian population, but this was not confirmed in subsequent studies. The purpose of this research was to investigate the association of 1484insG polymorphism of the PTP1B with obesity, insulin resistance, type 2 diabetes and other cardiovascular-related traits in an Iranian population.

Materials and Methods: The genotypes of 1484insG variant were determined by the PCR-RFLP method in 242 unrelated subjects, including 171 individuals with normal glucose tolerance and normal fasting glucose levels, and 71 type 2 diabetics. Insulin resistance was assessed using the homeostasis assessment model.

Results: The allelic frequency of the 1484insG polymorphism among type 2 diabetic patients and non-diabetic individuals was 6.3% and 3.8%, respectively (p=0.205). None of the subjects were homozygous for the 1484insG allele. Concerning quantitative traits in non-diabetic subjects, carriers of 1484insG allele had significantly higher body mass index (p=0.01), diastolic blood pressure (p=0.012), and HOMA-IR (p= 0.041) levels compared to those carrying the wild-type genotype. In type 2 diabetics, carriers of 1484insG allele had only significantly higher HOMA-B (P= 0/04) level compared to the individuals with the wild-type genotype.

Conclusion: Our results from a sample of Iranian type 2 diabetes cases and controls provide evidence that the 1484insG genotype of the PTP1B gene may be associated with obesity and insulin resistance.

Background and Aim: Malfunction in the energy homeostasis central system resulting from melanocortin receptor 4 (MC4R) mutations is considered to be an important factor in development of obesity. Although physical activity can weaken the effect of obesity-related genes, very few investigations have been carried out in relation to the MC4R gene. This study was conducted to investigate the association between physical activity and body mass index (BMI) in different MC4R genotypes (rs17782313).

Materials and Methods: A sample of 400 individuals was randomly selected from among subjects participating in the Iranian Multicenter Osteoporosis Study (IMOS). Their weights and heights were measured and their dietary intakes and physical activity data assessed using validated questionnaires. In addition, the different MC4R genotypes (rs17782313) were determined in the subjects by the PCR-RFLP method. Finally, using the adjusted multiple linear regression model, the probable effect of physical activity on BMI in different MC4R polymorphisms (rs17782313) was determined.

Results: Only in individuals with the CT genotype was a statistically significant association (p<0.05) observed between body mass index and physical activity (hr/d and METs-hr/wk).

Conclusions: Physical activity, particularly in heterozygous MC4R polymorphism individuals (rs17782313), can play an effective role in reducing body mass index.