rs344781

This review examines soluble urokinase plasminogen activator receptor (suPAR) as a biomarker of systemic chronic inflammation (SCI). The authors present 10 key properties supporting suPAR as a superior biomarker for measuring SCI, including its upregulation by immune activation, association with circulating immune cells, correlation with established inflammatory markers, stability over short-term influences, and prognostic value for morbidity and mortality across multiple diseases. A recent GWAS study identified 13 genome-wide significant variants associated with suPAR levels across 11 loci, including variants in PLAUR, PLAU, and PLA2R1 genes, with an estimated heritability of 60%. Specific PLAUR polymorphisms rs344781 and rs4251923 have been associated with various clinical conditions, and APOL1 variants interact with suPAR to influence kidney function.

This study examined variants in five genes encoding proteins in the MET receptor tyrosine kinase signaling pathway (MET, HGF, PLAUR, SERPINE1, SP1, SUB1) in 664 autism spectrum disorder (ASD) families (2,712 individuals including 1,228 with ASD) and 312 controls. Family-based association testing confirmed that the MET rs1858830 C allele was significantly associated with ASD (P=0.008), with stronger evidence in multiplex families (P=0.001), and showed a relative risk of 1.76 (95% CI: 1.19-2.62) for CC genotype. The PLAUR promoter variant rs344781 T allele also showed significant association with ASD (FBAT P=0.006, case-control P=0.007) with relative risks of 1.93-2.42, and demonstrated functional relevance through luciferase assays. Other genes in the pathway showed no significant associations.