Study of the association of Trp64Arg mutation of beta three adrenergic receptor with obesity in Saudi population

Abstract

Introduction: Beta three adrenergic receptor (ADRB3) is an adrenergic receptor that induces activation of adenylate cyclase located mainly in adipose tissue and is involved in the thermogenesis of brown fat tissue and in the regulation of lipolysis. Agonists of ADRB3 are found to induce the thermogenesis process of human brown fat tissue and thus believed to be excellent anti-obesity targets. The most studied single nucleotide polymorphism (SNP) of ADRB3 is rs4994. Inconsistent findings have been found in earlier studies about the association of rs4994 polymorphisms with obesity among different populations. The association of ADRB3/rs4994 polymorphism with obesity among the Saudi population is unknown. This study aimed to investigate the association of ADRB3/rs4994 polymorphism with obesity, blood lipids and blood pressure in the Saudi population. Method: This study was a case control study involving 88 obese healthy volunteers and 84 non-obese (controls) volunteers recruited from the King Khaled University Hospital (KKUH), Riyadh City, Saudi Arabia. Using KASPTM (Competitive Allele-Specific PCR) the rs4994 genotype for each participant was determined. The frequency, distribution, and association of each genotype with body mass index (BMI) and lipid profile were calculated. Results: The distribution of CC, TT and CT genotypes in the study population was 0.37, 0.06 and 0.56, respectively. The heterozygote CT genotype was associated with a reduced risk of obesity (odds ratio (OR)=0.4398, 95%CI=0.2338 to 0.8277, P-value=0.010). It was more frequent in the non-obese participants compared to the obese participants (67.9% vs. 44.3%, respectively). Moreover, participants with the CT genotype had a significantly lower BMI (P=0.004). In contrast, the CC genotype was associated with an increased risk of obesity (OR=2.5, 95%CI=1.3467 to 4.8758, P-value=0.004). The frequency of the CC genotype was higher in obese participants compared to the non-obese ones (46.6% vs. 28.6%, respectively). Participants with the CC genotype demonstrated a significantly higher BMI than participants with the CT or TT genotypes (Q= 4.5, P=0.004). The TT genotype had no significant effects on the participants’ BMI (OR=2.9, 95%CI=0.7563 to 11.5759, P value=0.11), and it was higher in obese compared to non-obese participants (9.1% vs. 3.6%, respectively). No significant effect of ADRB3/rs4994 polymorphism on blood lipid profile or blood pressure was observed. Conclusion: The findings of this study suggested that the heterozygote CT genotype of the ADRB3/rs4994 polymorphism is associated with a reduced risk of obesity among the Saudi population. In the future, larger scale studies are required to further confirm these observations.