The investigation of the relation of beta-2-receptor polymorphism with obesity and hypertension in patients with type 2 diabetes mellitus

Pharmacogenetics is the study of genetic variations that causea variable drug response characterized by alteration in drug metabolism orin pharmacodynamic. β2 Adrenoreceptor (B2AR) is a protein, which isexpressed widespread in the body and mediates catecholamine effectwithin several organs and tissues, that has insulin secretion and lipidstimulation as a result of its activation of catecholamines whilevasodilatation and bronchodilation are observed as primary effect whenstimulated. Functional mutations within the B2AR gene sequence havechanged the gene expression, down regulation, and coupling of thereceptor. One of the single nucleotide polymorphisms in the B2AR gene isGln27Glu; at codon 27 and results in the substition of Glutamine (Gln)amino acid to Glutamic (Glu) amino acid. These changes in the functions ofB2AR gene affect all physiological, biochemical, and pharmacological(cardiovascular) responses to ADRB2-mediated stimulation.It was shown that B2AR polymorphism plays a role in thedevelopment of respiratory diseases, and diseases such as congestiveheart failure, diabetes, obesity, and hypertension. In our case-controlstudy, we determined B2AR genotypes at codon 27 in 91 Type 2 DiabetesMellitus (DM) women and 66 healthy women controls to examine therelationship between these polymorphism and DM, obesity, andhypertension. Therefore, genomic DNA was amplified and genotyped usingAllele-Specific Polymerase Chain Reaction and Restriction FragmentLength Polymorphism assays, respectively. The healthy and patient groupsare strafied by three subgroups as Gln27Gln (wild), Gln27Glu(heterozygous) and Glu27Glu (mutant) according to their genotypes.The genotype frequencies of case and control groups werefound to be %13.2 and %18.2 for Gln27Gln genotype, %54.9 and %34.8for Gln27Glu genotype, %31.9 and %47 for Glu27Glu genotype,respectively. Gln27Glu genotype among the patients was more frequentthan the control group as statistically significant (p <0.005). The carriersof wild allele (Glu27) in the case group were significantly higher than thecontrol subjects with wild alelle(p <0.005). However, It was determinedthat the values for insulin, fasting blood glucose, and HOMA IR (InsulinResistance) of the patients who had Glu27glu (mutant) genotype werehigher than the ones with the other genotype. While the genotype andallele frequencies of obese diabetic patients(n=53, BMI>30kg/m2), werenot found statistically significant compared to control group. Moreover,neither BMI nor tension status (n=48, systolic blood pressure) did notappear to affect the development of diabetes mellitus (p>0.005). Ourresults showed that B2AR Gln27Glu polymorphism could form the basis forType 2 DM because it was related to the parameters such as fasting bloodglucose, insulin, HOMA IR that could pose risk for Type 2 DM, but was notrelated to development of obesity and hypertension in the DM.Key Words: Type2 Diabetes Mellitus, Obesity, Hypertension,pharmacogenetics, B2AR genetic polymorphism