PCSK9 Loss-of-Function Variants, Low-Density Lipoprotein Cholesterol, and Risk of Coronary Heart Disease and Stroke: Data From 9 Studies of Blacks and Whites.
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Kent Shia T, Rosenson Robert S, Avery Christy L, Chen Yii-Der I, Correa Adolfo, Cummings Steven R, Cupples L Adrienne, Cushman Mary, Evans Daniel S, Gudnason Vilmundur, Harris Tamara B, Howard George, Irvin Marguerite R, Judd Suzanne E, Jukema J Wouter, Lange Leslie, Levitan Emily B, Li Xiaohui, Liu Yongmei, Post Wendy S, Postmus Iris, Psaty Bruce M, Rotter Jerome I, Safford Monika M, Sitlani Colleen M, Smith Albert V, Stewart James D, Trompet Stella, Sun Fangui, Vasan Ramachandran S, Woolley J Michael, Whitsel Eric A, Wiggins Kerri L, Wilson James G, Muntner Paul
Аннотация
METHODS AND RESULTS: These 9 studies together included 17 459 blacks with 403 (2.3%) having at least 1 Y142X or C679X variant and 31 306 whites with 955 (3.1%) having at least 1 R46L variant. Unadjusted odds ratios for associations between PCSK9 LOF variants and incident coronary heart disease (851 events in blacks and 2662 events in whites) and stroke (523 events in blacks and 1660 events in whites) were calculated using pooled Mantel-Haenszel estimates with continuity correction factors. Pooling results across studies using fixed-effects inverse-variance-weighted models, PCSK9 LOF variants were associated with 35 mg/dL (95% confidence interval [CI], 32-39) lower LDL-C in blacks and 13 mg/dL (95% CI, 11-16) lower LDL-C in whites. PCSK9 LOF variants were associated with a pooled odds ratio for coronary heart disease of 0.51 (95% CI, 0.28-0.92) in blacks and 0.82 (95% CI, 0.63-1.06) in whites. PCSK9 LOF variants were not associated with incident stroke (odds ratio, 0.84; 95% CI, 0.48-1.47 in blacks and odds ratio, 1.06; 95% CI, 0.80-1.41 in whites).
CONCLUSIONS: PCSK9 LOF variants were associated with lower LDL-C and coronary heart disease incidence. PCSK9 LOF variants were not associated with stroke risk.