Differential effect of the allele G ADRB2 (rs1042714) and allele C ADRB3 (rs4994) and its association with metabolic-associated steatotic liver disease (MASLD) risk factors in Mexican population.

Introduction and Objectives

Adrenergic receptors (ADR) regulate adipocyte energy expenditure. G ADRB2 and C ADRB3 alleles are associated with fat deposition and metabolic alterations. The distribution of these polymorphisms and their influence on liver disease in Western Mexico are unknown.

Materials and Patients

In this cross-sectional study, we evaluated 919 unrelated adults with Caucasian ancestry (Villa Purificación, Los Altos, Cuquio), Native population (Nahuas, Huicholes), and Mestizo (admixed) (Guadalajara, Nayarit). Genomic ADN was extracted from leukocytes using the salting out method. ADRB2 and ADRB3 genotyping was performed using a Real-Time PCR system (TaqMan, Applied Biosystems, rs1042714 and rs4994). Body composition was assessed by bioelectrical impedance with an InBody analyzer (Inbody Co, Seoul, Korea). Biochemical tests included glucose, total cholesterol (TC), triglycerides (TG), high-density cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and very low-density lipoprotein cholesterol (C- VLDL). Insulin resistance (IR) was calculated as fasting plasma glucose (mg/dL) × fasting serum insulin (μU/mL)]/405 and defined as HOMA-IR ≥ 2.5. Statistical differences for quantitative and qualitative variables were analyzed using Student's t-test and Chi-square, respectively, with R study software. Hardy-Weinberg equilibrium (HWE) was obtained using Arlequin software (version 3.01).

Results

The Natives had the lowest frequency of the G ADRB2 allele (2.9%), while the Caucasians showed the highest frequency (21.2%). In the general population, the CG/GG genotypes were associated with a higher risk for increased VLDL [OR 1.98 (1.25-3.09 p=0.003)] and hyperglycemia [OR 1.91 (1.19-3.04 p=0.007)] than CC genotype carriers. Among the Caucasians, the CG/GG genotype was protective against increased LDL [OR 0.22 (0.05-0.81 p=0.023)]. The C ADRB3 allele was highest in native populations (23.7%), while the Caucasians showed the lowest frequencies (12.8%). In Natives, the C ADRB2 allele and C ADRB3 allele were associated with a higher risk of hypertriglyceridemia [OR 2.99 (1.16-9.37 p=0.036)] and hyperinsulinemia [OR 9.93 (1.68-189 p=0.035)] respectively. In the mestizo population, TC/CC genotype patients showed a higher risk of body fat [OR 2.26 (1.4-3.7 p=0.001)].

Conclusions

The frequency of allele G ADRB2 is higher than in those with Caucasian ancestry, while allele C ADRB3 is higher in the Native population. The G ADRB2 and allele C ADRB3 confer the risk of having higher body fat without metabolic alterations in Caucasian populations. The C ADRB2 allele and C ADRB3 allele confer risk for hyperinsulinemia and hypertriglyceridemia in Native populations, metabolic alterations that have been associated with MASLD.

Ethical statement: The Institutional Review Board approved this study, and participants signed a written informed consent before entry.

Declaration of interests: None.

Funding: University of Guadalajara-Programa de Fortalecimiento de Institutos, Centros y Laboratorios.