FABP-2 and PPAR-γ Haplotype as Risk Factors for Dyslipidemia in a Type 2 Diabetes Mellitus Population of Santa Rosa del Conlara, San Luis, Argentina

Abstract

Introduction: Type 2 Diabetes Mellitus (T2DM) is a complex disorder caused by the interaction between genetic predisposition and environmental factors. Genetics plays an important role on lipid homeostasis. Many genes are involved in the lipid metabolism, such as FABP-2 and PPAR-γ. Aim: To evaluate the association between specific SNPs and haplotypes of the FABP-2 and PPAR-γ genes with T2DM and lipid profile in an Argentinean population. Methods: The FABP-2 (rs1799883) and PPAR-γ (rs1801282) polymorphisms were genotyped and analyzed in association with lipid profile and T2DM, separately and also combined in haplotypes. Results: The frequency of the rare Thr54 allele of the FABP-2 polymorphism in control (0.33) was not different from the frequency in T2DM (0.27), whereas the frequency of the rare Ala12 allele of the PPAR-γ polymorphism in control was different from the frequency in T2DM (0.26 and 0.14, respectively; p = 0.0031). Frequencies of haplotypes for these two single-nucleotide polymorphisms differed significantly in control and T2DM. Haplotype association analysis showed the associations between ThrPro haplotype and TG levels (OR = 2.520; 95% CI = 1.139 - 5.575; p = 0.027) and between ThrPro haplotype and TC and LDL-c levels when compared to AlaPro haplotype (difference = 0.175, 95% CI = 0068 - 0.499, p < 0.0001; difference = 0.052, 95% CI = 0.017 - 0.158, p < 0.0001, respectively). Conclusions: These results from a haplotype analysis show for the first time that genetic combinations of alleles of the FABP-2 and PPAR-γ gene could play a role in the susceptibility to develop dyslipemia in T2DM.