Northern Chinese Han populations with sporadic Alzheimer's disease and the role of urokinase-type plasminogen activator gene promoter polymorphisms

BACKGROUND: Polymorphisms of urokinase-type plasminogen activator gene (PLAU) have recently been reported to be associated with sporadic Alzheimer disease (SAD). However, most studies have focused on the exon region of this gene, and there is no report on the association between promoter polymorphisms of the PLAU and SAD. OBJECTIVE: To determine whether SAD is associated with promoter polymorphisms of PLAU in Northern Han Chinese. DESIGN, TIME AND SETTING: A case-control study was performed at Neurology Laboratory of Xuanwu Hospital of the Capital Medical University from September 2006 to July 2008. PARTICIPANTS: A total of 397 participants living in Beijing were assigned to SAD [n = 196, including 103 males and 93 females, mean age of (64 +/- 7) years] and control [n = 201, including 108 males and 93 females, mean age of (68 +/- 6) years] groups. The patients were diagnosed and met the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorder Association criteria for possible Alzheimers disease. Controls received clinical, mental, and neurological examinations to rule out cognitive deficiencies. All controls had Mini-Mental Status Examination scores > 27. METHODS: Genotypes of PLAU and apolipoprotein-E were examined in 196 patients with SAD and 201 age- and sex-matched controls from the same community using polymerase chain reaction-restriction fragment length polymorphism method. SPSS 11.5 software was used for data analysis, distribution of allele and genotypic frequency were calculated, and Hardy-Weinberg was also performed in this study. MAIN OUTCOME MEASURES: The main outcome measures were allele and genotype frequency differences in the promoter region of the PLAU gene between SAD and control subjects. RESULTS: In Chinese Han populations, the two polymorphisms in PLAU promoter were -25 C/T (rs2227579) and 43 G/T (rs2227580). Detection of these promoter polymorphisms revealed significant differences in allele and genotype frequency for -25 C/T and 43 G/T when 196 SAD patients were compared with 201 controls (P <= 0.05). Logistic analyses indicated that, compared with C/T and T/T genotypes, the -25 C/C genotype resulted in a 1.5-fold risk for developing SAD (adjusted odds ratio = 1.510, 95% confidence interval: 0.198-2.281, P = 0.010), while the 43G/G genotype resulted in a 1.3-fold risk for SAD (adjusted odds ratio = 1.300, 95% confidence interval: 0.178-2.051, P = 0.030). CONCLUSION: The present study provided evidence that promoter polymorphisms of PLAU are associated with development of SAD in Northern Han Chinese.