P2RY12:rs7637803 TT variant genotype increases coronary artery aneurysm risk in Kawasaki disease in a southern Chinese population

• Published in: The journal of gene medicine 2019-01, Vol.21 (1), p.e3066-n/a
• Main Authors: Lu, Zhaoliang, Xu, Yufen, Fu, Lanyan, Tan, Yaqian, Che, Di, Huang, Ping, Pi, Lei, Zhou, Huazhong, Liang, Xiaoyun, Zhang, Li, Gu, Xiaoqiong
• Format: Article
• Language: English
• Subjects: Alleles; Aneurysm; Aneurysms; Asian Continental Ancestry Group - genetics; Case-Control Studies; Child, Preschool; Children; Coronary Aneurysm - diagnosis; Coronary Aneurysm - epidemiology; Coronary Aneurysm - etiology; Coronary artery; coronary artery aneurysm; Coronary vessels; Female; Gene Frequency; Gene polymorphism; Gene therapy; Genetic Predisposition to Disease; Genotype; Genotype & phenotype; Humans; Infant; Infant, Newborn; Kawasaki disease; Male; Mucocutaneous lymph node syndrome; Mucocutaneous Lymph Node Syndrome - complications; Mucocutaneous Lymph Node Syndrome - epidemiology; Mucocutaneous Lymph Node Syndrome - genetics; Odds Ratio; P2RY12; Platelets; Polymorphism, Single Nucleotide; Receptors, Purinergic P2Y12 - genetics; Severity of Illness Index; Thrombosis
• ISSN: 1099-498X; 1521-2254
• DOI: 10.1002/jgm.3066

Background Activated‐platelet increases the risk of thrombosis in Kawasaki disease (KD) patients with a coronary artery aneurysm (CAA). The ADP pathway is one of the platelet activation and aggregation pathways. The P2RY12 gene encodes the ADP receptor that is highly concentrated on platelets. However, few studies have reported on P2RY12 in relation to KD susceptibility with or without CAA. Methods We recruited 1335 healthy controls and 776 KD patients, including 103 with CAA, and selected five P2RY12 polymorphisms: rs9859538, rs1491974, rs7637803, rs6809699 and rs2046934. The present study focused on the relationship between the P2RY12 polymorphisms and KD with or without CAA. Results Among all of the selected polymorphisms, single‐locus analysis showed no significant association between the P2RY12 polymorphism and KD susceptibility. However, we found a significant relationship between rs7637803 and CAA risk in KD patients [CT versus CC: odds ratio (OR) = 0.41, 95% confidence interval (CI) = 0.22–0.75; p = 0.0041; TT versus CC: OR = 2.90, 95% CI = 1.12–7.46; p = 0.0276]. Stratification analysis by age in KD patients indicated that the rs7637803 TT genotype increased CAA formation risk among children aged (OR = 3.90, 95% CI = 1.42–10.69; p = 0.0081) and increased the onset risk of CAA in males (OR = 6.28, 95% CI = 2.01–19.65; p = 0.0016). The combined effect of the five selected P2RY12 risk genotypes with the KD patients compared to non‐mutated P2RY12 genotypes (score: 0) showed that patients with P2RY12 genotype polymorphisms (score: 1–5) had a significantly increased CAA risk (p = 0.0086). Stratification analysis for the severity of CAA found that the rs7637803 TT genotype reduced giant CAA (GCAA) risk (OR = 4.60, 95% CI = 1.70–12.41; p = 0.0026). Conclusions The results of the present study indicate that the P2RY12 rs7637803 genotype might be used as a biomarker to predict the occurrence of GCAA.