ITPKC polymorphism (rs7251246 T > C), coronary artery aneurysms, and thrombosis in patients with Kawasaki disease in a Southern Han Chinese population

Abstract

ObjectivesKawasaki disease (KD) is a commonly acquired pediatric systemic vasculitis disease resulting in coronary artery aneurysm (CAA). The relationship between the ITPKC polymorphism (rs7251246) and the severity and susceptibility to KD in the Han Chinese population in Southern China remains unclear.MethodsWe enrolled 262 children as controls and 221 children with KD (46 [20.8%] with intravenous immunoglobulin resistance and 82 [37.1%] with CAA). The relationship between the ITPKC rs7251246 polymorphism, KD susceptibility, and CAA formation was investigated.ResultsWhile the ITPKC rs7251246 T>C polymorphism was not significantly associated with KD susceptibility, it was significantly related to the CAA risk in children with KD [CC/CT vs. TT: adjusted odds ratio [OR] 2.089, 95% confidence interval [CI] 1.085–4.020]. Male children with the rs7251246 CT/TT genotype had a significantly lower risk of thrombosis [CT/TT vs. CC: adjusted OR 0.251, 95% CI 0.068–0.923]. Children with KD, especially those with CAA, had significantly downregulated ITPKC mRNA compared to healthy children. ITPKC mRNA levels were lower in children with CAA who developed thrombosis (P=0.039). In children with KD, the CC genotype showed lower mRNA levels of ITPKC (P=0.035).ConclusionThe ITPKC rs7251246 T>C polymorphism may be a risk factor for CAA and thrombosis in children with KD in the Han Chinese population, likely due to differences in mature mRNA levels caused by interference of RNA splicing. Dual antiplatelet therapy for thrombosis is recommended for male children with the rs7251246 CC genotype.

Pharmacogenomics of Coronary Artery Response to Intravenous Gamma Globulin in Kawasaki Disease

“…We used strict criteria for IVIG treatment in our study subjects in accordance with pharmacogenomics design. Accordingly, our results using different design and methodology did not replicate findings from prior studies such as associations with coronary aneurysms for variants in ITPKC 55 , KCNN2 54 , NEBL and TUBA3C 51 , SLC8A1 57 , and the matrix metalloproteinase ( MMP ) gene family 58 .…”

“…Prior studies, which have identified numerous significant variants associated with coronary aneurysms, did not account for the IVIG therapeutic effect. 53 54,55 Clinical trials clearly show that IVIG reduces the risk of CAA. 56 However, those previous genetic studies for the most part do not clarify whether study participants received appropriate IVIG treatment.…”