Target gene variations of <i>PPAR</i> isoforms may contribute to MODY heterogeneity: a preliminary comparative study with type 2 diabetes

Abstract

Aims: The objective of this study was to evaluate the associations of several genetic variants of peroxisome proliferator-activated receptors (PPARs) on clinical and laboratory parameters in patients with maturity-onset diabetes of the young (MODY), and possible contribution to heterogeneity of the disease. Methods: The study groups comprised patients with MODY (genetically confirmed (n = 28), clinically relevant but genetically unconfirmed;MODYX (n = 56)), type 2 diabetes mellitus (T2DM;n = 94) and healthy controls (n = 153). PPARA-L162V-(rs1800206), PPARG-C161T-(rs3856806), P12A-(rs1801282), and PPARB/D + 294 T/C(rs2016520) polymorphisms were genotyped by real-time-PCR. Results: The results demonstrated that the frequencies of PPARA-LL162 (p = 0.002), PPARG-CC161 (p = 0.002), and PPARG-ProPro (p = 0.012) genotypes were significantly higher in the MODY group compared to the controls. Furthermore, total-MODY and MODYX groups had a higher frequency of PPARA-LL162 genotype than T2DM (p = 0.005 and p = 0.006, respectively). The frequency of the PPARB/D + 294 T allele was significantly higher in individuals with T2DM than in genetically-determined MODY group (p = 0.019). The PPARA-LL162 genotype was associated with early-onset diabetes in total-MODY (p = 0.022) and T2DM (p < 0.05) groups. Conclusions: The association of PPARA-L162V polymorphism with early-onset diabetes in both T2DM and MODY is a noteworthy finding. Considering these results, we suggested that genetic polymorphisms in PPAR isoforms may contribute to the clinical and metabolic heterogeneity of MODY.