The Polymorphism of Metabolic and Immune Mechanisms Controlling Genes in Type 2 Diabetes Mellitus.

Background/Objectives: Most genes involved in the pathogenesis of Metabolic Syndrome (MS) and Type 2 Diabetes Mellitus (T2DM) are regulated by peroxisome proliferator-activated receptors (PPARs), which modulate the production of pro-inflammatory cytokines, with interleukin-6 (IL-6) playing a crucial role. The associations of single-nucleotide polymorphisms (SNPs) with MS and T2DM remain uncertain across populations. Therefore, we aimed to investigate the associations of PPAR-related SNPs in IL-6, LEP, ADIPOQ, ADIPOR1, and ADIPOR2 with MS and T2DM clinical features. Methods: Polymorphism analysis of IL-6, LEP, ADIPOQ, ADIPOR1, and ADIPOR2 genes was performed on isolated DNA from individuals diagnosed with T2DM and from healthy controls using real-time polymerase chain reaction (qPCR). Results: The IL-6-174G/C polymorphism shows that the CC genotype is associated with higher MS risk, whereas the GG genotype appears protective against metabolic disturbances. When the IL6 CC genotype is combined with ADIPOR2 GA or ADIPOR2 219 A/T, hyperglycemia is 1.3 times more frequent than with other IL6/ADIPOR2 genotype combinations. Conclusions: To develop informative genetic risk scores, future studies should include additional polymorphisms in key immune-metabolic pathway genes, such as AP-1, NF-κB, and FFAs.