Effect of the combination of the variants -75G/A APOA1 and Trp64Arg ADRB3 on the risk of type 2 diabetes (DM2).

Objective: Numerous genes have been associated with the risk for type 2 diabetes mellitus (DM2). In an attempt to understand how specific variants of different genes interact and intervene in the molecular and physiological mechanisms of disorders such as diabetes or insulin resistance, the search for gene-gene interactions is constantly growing. We searched for a possible interaction between two polymorphisms (Trp64Arg of ADRB3 gene and -75G/A of APOA1gene) and the risk for DM2 in a population from southern Spain.
Design and Methods: A cross-sectional study in southern Spain of 1020 people, aged 18-65 years. All persons underwent a clinical, anthropometrical and biochemical evaluation, including an oral glucose tolerance test (OGTT). Insulin resistance was measured by homeostasis model of assessment (HOMA). The polymorphisms -75G/A of APOA1 and Trp64Arg of ADRB3 were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and real-time PCR, respectively.
Results: The genotype frequencies of the -75G/A polymorphism of the APOA1 gene were 62.7% GG, 25.7% GA and 11.6% AA, whereas for the Trp64Arg polymorphism of the ADRB3 gene, they were 87.5% Trp/Trp, 11.7% Trp/Arg and 0.8% Arg/Arg. Subjects with both gene variants had a greater odds ratio (OR) of having DM2 [OR = 5.5; 95% confidence interval (CI) = 1.2-23.5] than persons with one or none of the variants, after adjusting for age, sex, body mass index (BMI) and homeostasis model assessment of insulin resistance (HOMA-IR).
Conclusions: Joint association of allele -75A (APOA1) and allele Arg64 (ADRB3) increase the risk of DM2 in a population from southern Spain.