Polymorphic variants of the beta2-adrenergic receptor (ADRB2) gene and ADRB2-related propanolol-induced dyslipidemia in the Colombian population

Different polymorphisms of the ADRB2 gene encoding the β2-adrenergic receptor (ADRB2) are associated with changes in a variety of responses of the sympathetic nervous system (SNS). In this study, we have investigated the distribution of frequencies of ADRB2-relaled allelic variants (Arg 16 Gly, Gln 27 Glu, Thr 164 Ile) in the Colombian population, as well as the influence of the Gln 27 Glu polymorphism as a risk factor for the development of dyslipidemia following propranolol administration. Genotyping was performed in unrelated Colombian volunteers, using PCR-RFLP methods. To examine the association between the Gln 27 Glu polymorphism of the ADRB2 gene and dyslipidemia induced by propranolol, we recruited 19 healthy individuals who were homozygous for either the Gln 27 (wild-type, N = 11) or the Glu 27 (homozygous mutant, N = 8) genotype. Electrocardiography (ECG), heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), serum lipid levels (T-CHO, HDL-CHO, TG), and fibrinogen were determined before and after propranolol administration. The distribution of genotypes was as follows: Arg 16 Arg 46%, Arg 16 Gly 47.4%, Cly 16 Gly 6.6%, Gln 27 Gln 44.7%, Gln 27 Glu 48.2%, and Glu 27 Glu 7.1%, with allelic frequencies of 69.7% for Arg 16 , 30.3% for Gly 16 , 68.8% for Gln 27 , and 31.2% for Glu 27 . The Thr 164 Ile polymorphism was found only in one subject, who was heterozygous for the isoleucine variant. Significant changes in physiological parameters (HR, SBP, DBP) have been found in association with ADRB2 variants in both native and mutant subgroups after propranolol intake. HDL-CHO levels diminished (p = 0.005) in native homozygous individuals (Gln 27 Gln). whereas TG levels were found increased (p = 0.012) in the mutant homozygous individuals (Glu 27 Glu). T-CHO levels and serum fibrinogen levels remained unaltered in both subgroups. The evidence that subjects homozygous for Gln 27 in the ADRB2 gene show a significant reduction of HDL-CHO levels, as well as the increased TG levels in subjects homozygous for Glu 27 after propranolol administration, suggest that the Gln 27 Glu polymorphism represents a risk factor for dyslipidemia induced by propranolol. These results may contribute to a better understanding of the mechanisms underlying dyslipidemia induced by ADRB2 antagonists.