Recent genome-wide association study associated rs556621 on chromosome 6p21.1 with the risk of large artery atherosclerotic (LAA) stroke in Caucasians. However, subsequent replicate studies showed conflict results in different ethnicities. This study aimed to evaluate whether rs556621 was associated with LAA stroke in Chinese Han population. In this case–control study, 659 patients with LAA stroke and 650 healthy controls were enrolled. Associations between rs556621 genotypes and LAA stroke were analyzed with logistic regression model. Rs556621 variants were associated with increased risks of LAA stroke (codominant model: OR 1.42; 95 % CI 1.01–1.99; P = 0.010; recessive model: OR 1.40; 95 % CI 1.05–1.86; P = 0.003). When subjects were stratified by sex, TT genotype of SNP rs556621 was associated with an increased risk of LAA stroke in female when tested with recessive model (OR 2.36; 95 % CI 1.28–4.36, P = 0.006). In male subjects, however, no significant association was detected. Smoking status, sex did not significantly influence the relationship between genotypes of rs556621 and risk of LAA stroke (Pinteraction = 0.140, Pinteraction = 0.076). Rs556621 may play an important role in the development of LAA stroke in female Chinese of Han ethnicity. Larger studies with subjects of different ethnicities are warranted to confirm these findings.
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