Two Novel SNPs in the PLCL2 Gene Associated with Large Artery Atherosclerotic Stroke Identified by Fine-Mapping.

A genome-wide association study (GWAS) reported that the single nucleotide polymorphism (SNP) rs4618210 in the PLCL2 gene is related to myocardial infarction (MI) in the Japanese population, but no study has examined the correlation of PLCL2 with ischemic stroke (IS). The present study was designed to investigate whether the genetic variation in PLCL2 is associated with large artery atherosclerotic (LAA) stroke in a Han Chinese population. Tagging SNPs (tSNPs) of the PLCL2 gene were determined by a fine-mapping strategy and were genotyped by improved multiplex ligation detection reaction (iMLDR) technology in 669 LAA stroke patients and 668 healthy controls. A logistic regression model was used to analyze the associations between genetic variation at PLCL2 and the risk of LAA stroke. Two SNPs were significantly associated with the risk of LAA stroke after adjusting for potential confounders: for rs4685423, the AA genotype and CA genotype decreased the risk of LAA stroke compared with the CC genotype (multivariate-adjusted, P = 0.001); for rs4618210, the AA genotype and GA genotype decreased the risk of LAA stroke compared with the GG genotype (multivariate-adjusted, P = 0.007). In addition, haplotype analysis indicated that compared with haplotype TTT, haplotype TAT decreased the risk of LAA stroke in block 2 (adjusted OR, 0.706; 95% CI, 0.550-0.907; P = 0.006). The analysis of SNP-SNP interactions showed that rs4685423 was the most influential contributor to LAA stroke risk. SNPs rs4685423 and rs4618210 in the PLCL2 gene may be related to the risk of LAA stroke in Han Chinese.

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