Association of Variants and Haplotypes in ADIPOQ, and Serum Adiponectin Levels with Metabolic Syndrome and Its Components in Mexican Adolescents.

Abstract

Background: Variants in ADIPOQ may affect gene expression and serum adiponectin levels (SAL), contributing to the development of metabolic syndrome (MetS) components and cardiometabolic disorders in Mexican adolescents.

Aim: To evaluate the association of the genetic variants rs266729, rs822396, rs2241766, and rs1501299 in ADIPOQ, their haplotypes, and SAL with MetS components and cardiometabolic parameters in adolescents from western Mexico.

Materials and methods: A total of 494 adolescents from Jalisco, Mexico, aged 10-17 years, were studied. The biochemical and clinical characteristics of cardiometabolic disorders were diagnosed based on age-, sex-, and population-specific percentiles. Peripheral blood samples were obtained. Serum was separated and SAL were measured by ELISA. DNA was extracted and genotyped using real-time polymerase chain reaction for allelic discrimination. Hardy-Weinberg equilibrium was assessed, and associations were analyzed using logistic regression and Spearman correlations, with a 95% statistical confidence level.

Results: SAL were lower in adolescents with MetS (P = 0.03) and low high-density lipoprotein (P = 0.01). The rs266729G allele was associated with very low-density lipoprotein >30 mg/dL in the additive inheritance model [AIM; odds ratio (OR) = 1.59, 95% confidence interval (CI) = 1.01-2.53, P = 0.04], dominant inheritance model (DIM; OR = 2.26, 95% CI = 1.07-4.73, P = 0.03), and codominant inheritance model (OR = 2.23, 95% CI = 1.03-4.81, P = 0.04). The rs822396G allele was associated with decreased SAL in AIM (OR = 5.00, 95% CI = 1.69-14.7, P = 0.004) and DIM (OR = 5.23, 95% CI = 1.41-21.6, P = 0.01). The rs2241766G allele (recessive model) was associated with increased alanine aminotransferase levels (OR = 3.73, 95% CI = 1.10-12.6, P = 0.03) and correlated with higher SAL (R = 0.202, P = 0.045). In controls, the haplotype rs822396-rs2241766-rs1501299 is in linkage disequilibrium (D' = 1), but the correlation is low (R² < 0.1), while in MetS adolescents, D' was incomplete. Several haplotypes were associated with cardiometabolic parameters.

Conclusion: The variants in ADIPOQ, are associated with MetS and low SAL. The rs822396G allele appears to be a key factor for low SAL and its association with cardiometabolic parameters. The rs2241766T allele was linked to low SAL and clinical characteristics of MetS.