Pentanucleotide TTTTA Repeat Polymorphism of Apolipoprotein(a) Gene and Plasma Lipoprotein(a) Are Associated with Ischemic and Hemorrhagic Stroke in Chinese: a Multicenter Case-control Study in China

Background And Purpose: It is still inconclusive whether high plasma lipoprotein(a) [Lp(a)] level is a risk factor for stroke. Small sample size and different ethnic groups and methodologies might be contributors to the conflicts in study results. The purpose of the present study was to investigate the association between plasma Lp(a) levels, pentanucleotide TTTTA repeat (PNTR) polymorphism of the apolipoprotein(a) [apo(a)] gene, and Chinese stroke in a case-control study.

Methods: We recruited 1825 cases with stroke (44.3% cerebral atherothrombosis, 28.3% lacunar infarction, and 27.3% intracerebral hemorrhage) and 1817 controls from 7 centers in China. Lp(a) concentrations were quantified by enzyme-linked immunosorbent assay. The PNTR polymorphism of the apo(a) gene was determined by polymerase chain reaction-polyacrylamide gel electrophoresis. Conditional multivariate logistic regression analysis was used to identify independent risk factors for stroke and its subtypes.

Results: Lp(a) levels were significantly higher in cases than in controls (median, 28.5 versus 23.1 mg/dL; P<0.001), leading to a 1.97-fold (95% CI, 1.64 to 2.37) increase in risk for overall stroke, 2.0-fold (95% CI, 1.59 to 2.52) increase for atherothrombotic type, 2.05-fold increase (95% CI, 1.59 to 2.63) for lacunar type, and 1.64-fold increase (95% CI, 1.21 to 2.21) for hemorrhagic type. The number of PNTR negatively correlated with Lp(a) levels. Low-number repeats (sum of both alleles <16) of apo(a) PNTR were associated with both atherothrombotic stroke (odds ratio, 1.41; 95% CI, 1.04 to 1.91) and hemorrhagic stroke (odds ratio, 1.62; 95% CI, 1.09 to 2.37).

Conclusions: Our results indicate for the first time that low numbers of apo(a) PNTR and plasma Lp(a) levels are independently associated with both ischemic and hemorrhagic stroke in Chinese.