QDPR rs3733570 polymorphism is associated with type 2 diabetes and diabetic kidney disease accompanied by...

Genetic factors play important roles in the development of type 2 diabetes mellitus and its complications. Diabetic kidney disease, a common microangiopathic complication of diabetes, is linked to an increased risk of major cardiovascular events and overall mortality. Tetrahydrobiopterin deficiency is implicated in DKD pathogenesis, and the QDPR gene is critical for maintaining BH4 homeostasis. The present study was designed to screen single nucleotide polymorphisms in the QDPR coding region, and assess their associations with T2DM and DKD.

Genetic analysis for SNPs in the coding region was conducted using a systematic screening approach. Direct sequencing and statistical analysis tools were employed to identify potentially functional SNPs. Following this, rs3733570 was selected based on its potential biological relevance and frequency in the target population. A total of 1,844 participants from Kai Luan General Hospital (Tangshan, China) were included for validation. Genotyping of QDPR rs3733570 was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 690 healthy controls, 818 patients with T2DM, and 336 patients with DKD.

Regression analysis showed that the rs3733570 AA genotype was associated with increased risk of T2DM (OR = 1.33, 95% CI: 0.99-1.79, p < 0.05). In stratified analysis, carriers of the AA genotype with dyslipidemia had a higher risk of DKD (OR = 1.80, 95% CI: 1.03-3.16, p < 0.05).

The QDPR rs3733570 AA genotype may increase susceptibility to T2DM and, in the presence of dyslipidemia, to DKD in the Chinese Han population. After adjustment, the AA genotype showed a borderline association with T2DM risk (OR = 1.33, 95% CI: 0.99-1.79, p = 0.057).