Purinergic receptor P2Y, G-protein coupled, 2 (P2RY2) gene is associated with cerebral infarction in Japanese subjects

Abstract

G-protein-coupled purinergic receptor P2Y2 (P2RY2) has an important role in the process of atherosclerosis related to cerebral infarction (CI). The aim of this study was to investigate the relationship between the P2RY2 gene and CI through a haplotypebased case-control study, including the separate analysis of two gender groups. A total of 237 CI patients and two control groups (control 1, 254; control 2, 255) were genotyped for five single nucleotide polymorphisms (SNPs) in the human P2RY2 gene (rs4944831, rs1783596, rs4944832, rs4382936, rs10898909). Among women, the distribution of the dominant rs4944832 phenotype (GG vs. GA+AA) differed significantly between the CI patients and the control 1 group (P¼0.043) and between the CI patients and the control 2 group (P¼0.029). Logistic regression analysis showed that the GG genotype of rs4944832 was significantly more prevalent in the female CI patients than in the control 1 (P¼0.021) and control 2 groups (P¼0.005). For all subjects, the overall distribution of the haplotype established by rs1783596-rs4382936-rs10898909 was significantly different between the CI patients and the control 1 group (P¼0.027). For all subjects, the frequency of the T-A-G haplotype (rs1783596-rs4382936-rs10898909) was also significantly higher (P¼0.031), whereas the frequency of the T-C-G haplotype (rs1783596-rs4382936-rs10898909) was significantly lower (P¼0.029) in the CI patients than in the control 1 group. The present results indicate that the T-A-G haplotype of the human P2RY2 gene is a susceptibility haplotype for CI in Japanese subjects, and that the GG genotype is a genetic marker for CI, particularly in Japanese women.

Bioinformatics analysis of differentially expressed genes in non alcoholic fatty liver disease using next generation sequencing data

“…[624] and Matejas et al [625] showed that EGR1, NR4A1, SIK1, CCN1, CEBPD (CCAAT enhancer binding protein delta), SOCS2, RGS2, KL (klotho), SOCS3, MMP1, CXCR4, CCN2, FST (follistatin), OGN (osteoglycin), CTLA4, KLF4, PTGER3, HBEGF (heparin binding EGF like growth factor), CCL2, OSM (oncostatin M), ERBB4, TNFSF11, MSTN (myostatin), ADAMTS1, CALCR (calcitonin receptor), INHBB (inhibin subunit beta B), EPO (erythropoietin), IL10, CEBPB (CCAAT enhancer binding protein beta), FOXO1, DKK1, GAS1, NPHP3, FGF2, ATF3, ANGPT2, SOCS1, IL1RAP, C9ORF72, BASP1, AKR1B10, SLC22A12, ACHE (acetylcholinesterase), TREM2, SCD (stearoyl-CoA desaturase), GCK (glucokinase), FOXP3, SLC22A2, EPHB2, LPL (lipoprotein lipase), ANGPTL8, HCN2, HSPA8, MB (myoglobin), KCNJ11, GLIS2, TNFSF13, LSS (lanosterol synthase), GAS6, AGRN (agrin), ACE2, NLRP6, DPEP1, TIMP3, CHI3L1, RASAL1, FAT1, GPBAR1, TREH (trehalase), CFB (complement factor B), FNDC5, HLA-G, MMP9, C4A and LAMB2 were associated with kidney disease, but these genes might be novel targets for NAFLD. [657], SOCS3 [658], MMP1 [659], CXCR4 [660], RASD1 [661], SLC7A11 [662], OGN (osteoglycin) [341], KLF4 [663], IL1RL1 [664], CCL2 [665], EPO (erythropoietin) [666], IL10 [667], ESR2 [668], VIP (vasoactive intestinal peptide) [669], FOXC1 [670], FOXO1 [671], S100B [672], DKK1 [673], SOCS1 [674], C9ORF72 [675], CTCFL (CCCTC-binding factor like) [676], S1PR2 [677], ACHE (acetylcholinesterase) [678], TREM2 [679], EPHB2 [680], LPL (lipoprotein lipase) [681], P2RY2 [682], ACE2 [683], CHI3L1 [684], HLA-G [685] and MMP9 [686] are found in cerebrovascular diseases, but these genes might be novel targets for NAFLD.…”

Population-Specific Associations of Deleterious Rare Variants in Coding Region of P2RY1–P2RY12 Purinergic Receptor Genes in Large-Vessel Ischemic Stroke Patients

“…Different coding and non-coding SNPs (mostly common type) in P2RY1 and P2RY12 were previously evaluated in various IS population, however, the reported results have been conflicting so far [ 16 , 17 , 18 , 19 ]. It is worth mentioning that the possible associations of P2RY12 genetic variants, in a “gain-of-function” haplotype H2 of P2Y12 , with thromboembolic events (myocardial infarction (MI), IS, or deep venous thromboembolism/pulmonary embolism (DVT/PE)), were not confirmed in a prospective analysis of 14,916 initially healthy American men [ 17 ].…”

“…No previous studies addressed the impact or association of rare damaging polymorphisms in P2RY genes and IS. On the other hand, different SNPs (mostly common type) in P2RY1 and P2RY12 were previously evaluated in various IS cohorts, however, the reported results have been conflicting so far [ 16 , 17 , 18 , 19 , 20 ]. Out of all P2RY receptors, the greatest focus has been put on P2RY12 , which is expressed in megakaryocyte/platelet lineage, and contributes to progression of thrombosis and hemostasis to cerebrovascular events [ 23 ].…”

Danger signals in stroke

“…P2Y2R signaling contributes to chemotaxis of leukocytes to the site of tissue damage as well as differentiation and proliferation of cells important for wound healing. In a Japanese genomic analysis, a specific P2Y2 haplotype was associated with an increased risk of arteriosclerosis and cerebral infarction, especially in women (Wang et al, 2009). However, P2Y2R and P2Y6R both promote the phagocytic clearance of apoptotic cells or bacteria, thereby contributing to the termination of inflammation (Koizumi et al, 2007), but endothelial or epithelial expression of P2Y6R can also play a role in innate immune activation (Riegel et al, 2011).…”