Leptin receptors (LEPR) and beta3 adrenoreceptors (ADRB3) are involved in metabolic control and weight gain. ADRB3 TRP64ARG and LEPR Q223R polymorphisms increase the risk of obesity and type 2 diabetes (T2D) development. However, there is no data on combine effects of these two polymorphisms on the risk of overweight and T2D in patients of different sex and age that defined the goal of the study.
150 patients with T2D and 90 non-diabetic patients were enrolled in the study. Genomic DNA was extracted and amplified by polymerase chain reaction. We assessed the relationship between ADRB3 TRP64ARG (rs4994) and LEPR Q223R (rs1137101) genotypes in patients of different sex, age (with cut-off 55 years), body mass index (BMI) and T2D.
AG and GG genotypes in LEPR Q223R polymorphic site were associated with higher risk of T2D (OR=4.46, 95% CI 1.44-13.83, P=0.009) but not overweight in patients regardless of sexes and age (P=0,245). ADRB3 polymorphism was associated with increased risk of high BMI in females (P=0.01). At the same time rs4994 polymorphism (CT) demonstrated the protecting effect on T2D development (OR 2.27, 95%CI:1.02-5.05; P=0.044) mostly in females. CT genotype of ADRB3 TRP64ARG attenuated the effect of LEPR Q223R polymorphism on T2D risk in females (OR 0.1143, 95% CI 0.023-0.57; P=0.008) however this effect was more prominent in patients up to 55 years old.
ADRB3 TRP64ARG polymorphism was associated with overweight but decreased the risk of T2D development in females with LEPR Q223R polymorphisms under 55 years old.