A15374 Genetic Variant of Human Cholesterol Ester Transfer Protein (CETP) Raises HDL levels and Is Associated with Increased Risk for Large Vessel and Small Vessel Stroke in Chinese Patients

Abstract

Objectives: Cholesterol Ester Transfer Protein (CETP) mediates lipids transfer among lipoprotein particles, affects HDL levels in general population. The CETP deficiency mutation at CETP (442 D:G) raises HDL level. We set to access the association of raised HDL level and all stroke and major stroke subtypes in Chinese population. Methods: We carried out a case control study: INTERSTROKE-China study, with 3500 stroke cases and 3834 age/gender matched controls. Structured questionnaires were administered to each stroke cases and matched controls, and information of biometrics, socioeconomic status, lifestyle, biomarkers, etc, was obtained. Genotyping of the CETP deficiency mutation (CETP rs2303790) SNP was performed by the TaqMan Real Time PCR method. Results: We found that CETP G allele is associated with higher HDL levels (1.30 vs. 1.18 mmol, p = 7.8E-8 dominant), but not associated with all stroke OR 1.17 (95%CI; 0.95–1.46), even after adjustment for HDL level. In subtypes of stroke with CETP G allele, ischemic stroke showed positive association with OR 1.33 (1.05–1.69), but not hemorrhagic stroke with OR 0.99. We further test subtypes of ischemic stroke, and we found positive association of large vessel with OR 1.72 (1.06–2.62) and small vessel stroke with OR 1.38 (1.05–1.82) respectively. Borderline positive association was seen for subtypes of stroke with atrial fibrillation and cardiac cause. No hint of association was seen for encryptic stroke or cardioembolism. Conclusion: CETP genetic variant is association with raised HDL, but increased risk for large vessel and small vessel stroke, even after full adjustment for other stroke risk factors. We conclude that CETP variants raise HDL level also increase the risk for large and small vessel subtypes of ischemic stroke.