Association between osteoprotegerin gene polymorphisms and ischemic stroke etiological subtypes

Objective To investigate the relationship between osteoprotegerin (OPG) gene polymorphisms and ischemic stroke etiological subtypes, as well as the extent and distribution of cerebral atherosclerosis (AS) lesions. Methods Patients with ischemic stroke included 285 cases of large-artery atherosclerosis (LAA), 91 cases of small-artery occlusion (SAO) and 42 cases of purely AS, and 165 healthy controls were enrolled in this study. The LAA group was respectively divided into 3 subgroups according to the number and the distribution of stenostic vessels. Genotyping of three single nucleotide polymorphisms (SNPs; rs2073617, rs3134069, and rs3102735) in the promoter region of the OPG gene was performed by polymerase chain reaction-restriction fragment length polymorphism. Results Regarding the three SNPs of OPG gene, the frequence of genotype CC/CT and the prevalence of allele C of rs3102735 were higher in the LAA group contrasting with the control group (24.04% vs 14.85%, 44.21% vs 27.88%, χ2=10.758, 11.804, P=0.001, 0.024). However, comparisons of other frequences of genotypes or alleles did not reveal any significant differences among the LAA group, the SAO group, the AS group and the control group, as well as among different subgroups of LAA group. Haplotype analysis revealed that the frequencies of haplotype C-C-T in LAA group and SAO group were significantly lower(0.023, 0.017 vs 0.068, χ2=10.399, 5.841, P=0.001, 0.016), while that of haplotype T-A-C was significantly higher in SAO group(0.043 vs 0.016, χ2=4.708, P=0.030) compared with controls. Conclusions Our findings indicate that OPG gene polymorphisms might be associated with increased susceptibility to LAA ischemic stroke. But we fail to show association of OPG gene with the extent and distribution of AS. Key words: Osteoprotegerin; Polymorphism, single nucleotide; Haplotype; Brain infarction; Atherosclerosis