The association of PGC-1α and its single-nucleotide polymorphism with the lipid metabolic disorders of diabetic kidney disease in patients with type 2 diabetes

Aim: This study aimed to explore the correlation between peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and diabetic kidney disease (DKD) susceptibility in the Han Chinese population. Methods: The distribution of Gly482Ser (rs8192678) and its relationship with blood PGC-1α messenger RNA (mRNA) expression were examined in healthy volunteers, patients with type 2 diabetes mellitus (T2DM), and those with DKD. The single-nucleotide polymorphism was genotyped using a DNA extraction kit and TaqMan-minor groove binder (MGB) probe real-time polymerase chain reaction. Results: We enrolled 574 subjects: 212 healthy controls, 186 with T2DM, and 176 with DKD. The rs8192678 AA genotype was more frequent in controls than in T2DM or DKD groups (P < 0.001). Under additive, dominant, and recessive models, the GG genotype was linked to higher T2DM risk after age and sex adjustment (P < 0.001), but not to progression from T2DM to DKD. PGC-1α mRNA levels were also higher in AA carriers than in GG carriers across all groups (P < 0.05). Conclusion: Our study identifies the G allele of PPARGC1A rs8192678 as a risk factor for T2DM, but its role in DKD is context-dependent. Although not a risk factor in the general T2DM population, this allele is linked to higher DKD risk specifically in patients with normal triglyceride levels. This association was driven by the GA and AA genotypes, not the GG genotype, highlighting the complex interplay between genetics and metabolic state in DKD.