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

<b>Background/Objectives</b>: 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 <i>IL-6</i>, <i>LEP</i>, <i>ADIPOQ</i>, <i>ADIPOR1</i>, and <i>ADIPOR2</i> with MS and T2DM clinical features. <b>Methods</b>: Polymorphism analysis of <i>IL-6</i>, <i>LEP</i>, <i>ADIPOQ</i>, <i>ADIPOR1</i>, and <i>ADIPOR2</i> genes was performed on isolated DNA from individuals diagnosed with T2DM and from healthy controls using real-time polymerase chain reaction (qPCR). <b>Results</b>: The <i>IL-6-174G/C</i> polymorphism shows that the CC genotype is associated with higher MS risk, whereas the GG genotype appears protective against metabolic disturbances. When the <i>IL6</i> CC genotype is combined with <i>ADIPOR2</i> GA or <i>ADIPOR2</i> 219 A/T, hyperglycemia is 1.3 times more frequent than with other <i>IL6/ADIPOR2</i> genotype combinations. <b>Conclusions</b>: To develop informative genetic risk scores, future studies should include additional polymorphisms in key immune-metabolic pathway genes, such as <i>AP-1</i>, <i>NF-κB</i>, and <i>FFAs.</i>