Circulating protein Z concentration, PROZ variants, and unexplained cerebral infarction in young and middle-aged adults.
Protein Z (PZ) is a vitamin K-dependent plasma protein that exhibits both pro- and anticoagulant properties. Both low and high PZ levels have been linked to ischaemic stroke. Although PZ-lowering gene variants have been found to be less common in ischaemic stroke, the relationship remains unclear. We investigated PZ levels and PROZ variants in a multi-ethnic case-control study of unexplained stroke in participants aged 18 to 64. Plasma PZ was measured in cases (≥2 months post-stroke) and controls. PZ polymorphisms G79A (rs3024735) and A13G (2273971) were genotyped. A combined genetic score (0-4 minor alleles) was created assuming additive effects. A total of 715 individuals (1:1.4 cases:controls) was included. Analyses revealed evidence of a non-linear association. After adjusting for demographic and clinical covariates, PZ levels >2.5 µg/ml (90th%ile) were significantly associated with cryptogenic stroke (OR 2.41 [95 % CI 1.34, 4.34]) as compared with lower levels. Higher genetic score was related to progressively lower levels of PZ, and the presence of four minor alleles was associated with lower odds of stroke (adjusted OR 0.26 [95 % CI 0.07, 0.96]) versus 0 minor alleles. In this multi-ethnic study of young and middle-aged adults, there was evidence of a non-linear positive association between PZ level and unexplained stroke, with a directionally consistent association for genetic variants related to PZ levels and cryptogenic stroke. These findings support elevated PZ levels as a risk factor for cryptogenic stroke.
Lili
L
Zhang
Alan Z
AZ
Segal
Dana
D
Leifer
Roy L
RL
Silverstein
Linda M
LM
Gerber
Richard B
RB
Devereux
Dr. Jorge Kizer, Cardiovascular Clinical Research Unit, 1300 Morris Park Ave, Bronx, NY 10461, USA, Tel.: +1 718 430 2197, Fax: +1 718 839 7960, E-mail: jorge.kizer@einstein.yu.edu.
Jorge R
JR
Kizer
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001798:Blood Proteins / Q000032:analysis* / Q000235:genetics*; D016022:Case-Control Studies; D002544:Cerebral Infarction / Q000097:blood* / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009519:New York City / Q000453:epidemiology; D017711:Nonlinear Dynamics; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D055815:Young Adult
D001798:Blood Proteins; D005819:Genetic Markers; C026080:plasma protein Z
Biomarkers; genetic association studies; plasma protein Z; risk factors; stroke
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