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

Area of Science:

• Genetics and Neurology
• Molecular Biology

Background:

• Osteoprotegerin (OPG/TNFRSF11B) serum levels are elevated in ischemic stroke patients.
• A specific single nucleotide polymorphism (SNP), rs3134069, in the TNFRSF11B gene was previously linked to ischemic stroke in Italian diabetic patients.

Purpose of the Study:

• To investigate the association between the rs3134069 polymorphism and ischemic stroke in general Chinese Han populations.
• To determine if this association holds true in individuals without diabetes.

Main Methods:

• A case-control association study was conducted using two independent Chinese Han populations.
• Genotyping of rs3134069 was performed on 1629 cases and 1504 controls (China-Central) and 1206 cases and 720 controls (China-Northern).
• Expression quantitative trait loci (eQTL) analysis was performed.

Main Results:

• rs3134069 showed a significant association with ischemic stroke in both the China-Central (OR=1.50) and China-Northern (OR=1.53) populations.
• The association was consistently observed across combined populations (OR=1.41), males, females, and non-diabetic individuals.
• The minor allele C of rs3134069 was significantly associated with decreased TNFRSF11B expression (P=.002).

Conclusions:

• The single nucleotide polymorphism rs3134069 in the TNFRSF11B gene is a risk factor for ischemic stroke.
• Decreased expression of TNFRSF11B, influenced by rs3134069, contributes to the risk of developing ischemic stroke.