Objective:An association between a 3’ UTR polymorphism (G/A) in the transcription factor LBP-1c/CP2/LSF (CP2) gene and sporadic Alzheimer’s disease (AD) has been recently described. We have investigated the potential association of the CP2 polymorphism in a sample of sporadic, early- (EOAD) and late-onset AD (LOAD) cases and age- and sex-matched control subjects from Southern Italy. Design:Case-control study. Materials and Methods:We analyzed the genotype and allele distribution of CP2 and apolipoprotein E (APOE) polymorphisms in a cohort of 166 sporadic AD patients and 225 sex- and age-matched nondemented controls from Southern Italy population. The statistical analysis was performed by Pearson c2 (Hardy-Weinberg equilibrium), and Mann-Whitney test. The odds ratios (OR) and the 95% CI of AD between subjects with and without at least one A or G allele were calculated. The data were analyzed by SAS FREQ procedure (version 8.2). Exact tests were evaluated by Proc-StatXact (version 5.0). Results:We found that the CP2 A allele conferred an increased risk for AD in the whole sample (OR = 2.97), without interaction with APOE alleles. After stratification for the age at onset, this effect remained statistically significant only in early-onset AD patients (<70 years). Furthermore, AD patients with the A allele had a mean age at onset 3.2 years lower than those carrier of the G allele, but this difference did not reach statistical significance. Conclusion:This is the first report suggesting a risk of AD linked to the CP2 A allele, and the contrasting results of the present study are, at present, difficult to explain. However, the first study on this topic did not observe a significant protective effect of the A allele in the US population, and the different patterns of association between the CP2 polymorphism and AD might arise from the difference in genetic background among different populations. Furthermore, we hypothesize that the variability in the association between the A allele of the CP2 polymorphism and AD could be related to similar geographic variations in terms of CP2 allele or genotype frequency variability: from 0.09 to 0.05 of A allele frequency in UK, French, and North American healthy controls, only 0.02 in Southern Italy. Finally, it is possible that there is linkage disequilibrium with another biologically relevant locus on chromosome 12. The CP2 gene is a plausible position and functional candidate for influencing disease risk as it is located within the AD linkage region on chromosome 12, and it interacts with several genes, proteins and viruses that have been demonstrated to have a role in AD. In conclusion, our data support CP2 as a candidate gene for sporadic AD, suggesting further studies on larger, ethnically, and geographically different populations to better clarify the role of this gene in AD pathogenesis.
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