Recent evidence has suggested that down-regulation of somatostatin (SST) expression in the human brain during early stages of aging leads to an elevation in the steady-state levels of A beta and therefore may be involved in Alzheimer's disease (AD) progression. We hypothesized that alterations in the SST gene might after its expression or function and also play a role in the pathogenesis of sporadic AD (SAD). First, we sequenced the entire SST gene in 25 randomly selected controls and 25 SAD patients and then screened for C/T polymorphisms (rs4988514) in the 3' un-translated region. We genotyped rs4988514 polymorphisms as well as apolipoprotein epsilon 4 (APOE epsilon 4) status in 309 SAD patients and 276 normal controls with restriction fragment length polymorphism (RFLP) analysis. Results showed that the C allele of the rs4988514 polymorphism had an increased incidence in the SAD group compared to the control group (p = 0.042). In subjects with the APOE epsilon 4 allele, the presence of both the CC genotype and the C allele of this polymorphism were elevated in the SAD group compared to the control group (genotype p = 0.027. allele p = 0.011). In the whole study group, the age, sex, and APOE epsilon 4 adjusted OR for the risk of AD in C allele carriers was 1.313 (95%CI = 1.068-2.234, p = 0.027) whereas within only APOE epsilon 4 allele carriers, the adjusted OR increased to 2.734 (95%CI = 1.236-5.862, p = 0.012). Our results supported the notion that the C allele of the rs4988514 polymorphism may increase the risk for AD in the Chinese population and possibly have additive effect with the APOE epsilon 4 allele (c) 2009 Elsevier Ireland Ltd. All rights reserved.