Significant Association between OPG/TNFRSF11B Variant and Common Complex Ischemic Stroke.

BACKGROUND: The serum level of osteoprotegerin (encoded by OPG or TNFRSF11B) was previously shown to be increased in patients with ischemic stroke. A single nucleotide polymorphism rs3134069 in the TNFRSF11B gene was previously associated with ischemic stroke in a population of diabetic patients in Italy. It remains to be determined whether rs3134069 is associated with ischemic stroke in the general population or populations without diabetes.

MATERIALS AND METHODS: We genotyped rs3134069 and performed a case-control association study to test whether rs3134069 is associated with ischemic stroke in 2 independent Chinese Han populations, including a China-Central population with 1629 cases and 1504 controls and a China-Northern population with 1206 cases and 720 controls.

RESULTS: rs3134069 showed significant association with ischemic stroke in the China-Central population (P = 9.24 × 10-3 , odds ratio [OR] = 1.50). The association was replicated in the independent China-Northern population (P = 2.45 × 10-4 , OR = 1.53). The association became more significant in the combined population (P = 7.09 × 10-6 , OR = 1.41). The associations remained significant in the male population, female population, and population without type 2 diabetes. Our expression quantitative trait loci analysis found that the minor allele C of rs3134069 was significantly associated with a decreasedexpression level of TNFRSF11B (P = .002).

CONCLUSIONS: This study demonstrates that rs3134069 in TNFRSF11B increases risk of ischemic stroke by decreasing TNFRSF11B expression.