Association between P2RY12 Gene Polymorphisms and IVIG Resistance in Kawasaki Patients

Abstract

Children with Kawasaki disease (KD) resistant to intravenous immunoglobulin (IVIG) have a higher incidence of coronary artery lesions (CAL). Despite the association between Purinergic receptor P2Y12 (P2RY12) polymorphism, KD genetic susceptibility, and CAL complications being proved, few studies have assessed the relationship between P2RY12 polymorphisms and IVIG resistance in patients with KD. We recruited 148 KD patients with IVIG resistance and 611 with IVIG sensitivity and selected five P2RY12 polymorphisms: rs9859538, rs1491974, rs7637803, rs6809699, and rs2046934. A significant difference in the genotype distributions between patients was only observed for the rs6809699 A > C polymorphism (AC vs. AA: adjusted odds ratio (OR) = 0.48, 95% confidence interval (CI) = 0.27–0.84, P=0.011; AC/CC vs. AA: adjusted OR = 0.47, 95% CI = 0.27–0.83, P=0.0084). After adjusting for age and gender, the carriers of the rs6809699 C allele had OR of 0.44 to 0.49 for IVIG sensitivity (AC vs. AA: adjusted OR = 0.48, 95% confidence interval (CI) = 0.27–0.84, P=0.011; AC/CC vs. AA: adjusted OR = 0.47, 95% CI = 0.27–0.83, P=0.0084) compared to the carriers of a rs6809699 AA genotype, suggesting the protective effect of this SNP against IVIG resistance. Moreover, individuals with all five protective polymorphisms experienced a significantly decreased IVIG resistance compared to that of individuals with up to three protective polymorphisms (adjusted OR = 0.27, 95% CI = 0.13–0.57, P=0.0006). Our results suggest that the P2RY12 rs6809699 polymorphism could be used as a biomarker to predict IVIG resistance in KD patients.

Single-nucleotide polymorphisms of the SLC17A9 and P2RY12 genes are significantly associated with phantom tooth pain

“… 37 The rs3732759 SNP of the P2RY12 gene has been reported to be associated with clopidogrel sensitivity in patients with coronary artery disease. 38 The rs6809699 SNP and rs16863323 SNP in the LD block that also contains the rs3732759 SNP of the P2RY12 gene have been reported to be associated with intravenous immunoglobulin resistance in Kawasaki disease patients 39 and early neurological deterioration in acute ischemic stroke. 40 However, no previous studies have shown that the rs3732759 SNP of the P2RY12 gene and SNPs in the same LD block are associated with pain.…”

The Associated of the Risk of IVIG Resistance in Kawasaki Disease with ZNF112 Gene and ZNF180 Gene in a Southern Chinese Population

“…In the early years, our team has been focused on the progress of KD disease and the therapeutic effect, and achieved some exciting results. We found that single nucleotide polymorphisms (SNPs) of several genes (P2RY12, MRP4 and EIF2AK4 [35][36][37] ) were closely associated with IVIG treatment efficacy in KD; interestingly, these genes played important roles in immune response and cardiovascular-related functions. This study was the first one to focus on the effect of ZNF family (ZNF180 and ZNF112) on IVIG treatment resistance of KD.…”

P2 Receptors: Novel Disease Markers and Metabolic Checkpoints in Immune Cells

“…An association of other P2R SNPs with selected diseases was found, for example, the P2RY12 rs680969 SNP, which was proposed to predict resistance in child Kawasaki disease [ 158 ]. Other SNPs in P2RY12 were suggested to be predictive of cancer pain severity [ 159 ] or to contribute to interindividual variability in the response to the widely used antithrombotic agent cangrelor [ 160 ].…”