title: Association between promoter polymorphisms of the nicastrin gene and sporadic Alzheimer's disease in North Chinese Han population.
abstract: Increasing evidences have shown that nicastrin (NCSTN) plays a crucial role in gamma-cleavage of the amyloid precursor protein (APP). Inhibition of NCSTN demonstrated an altered gamma-cleavage activity, suggesting its potential implication in developing Alzheimer's disease (AD). We detected the NCSTN gene promoter region in 359 sporadic AD (SAD) patients and 331 controls and found three promoter single nucleotide polymorphisms (SNPs): -1216C/A (rs2147471), -796T/G (rs10752637) and -436C/T (rs1324738). For -1216C/A, there were significant differences in the allele and genotype frequency between AD and control subjects (allele P=0.031, genotype P=0.017). The allele and genotype frequencies remained significant before and after APOEvarepsilon4 stratification. The -1216CC carriers increased 2-fold risk for the development of SAD compared to the carriers with -1216CA and AA genotypes (OR=2.049, 95%CI=1.410-2.976, P=0.000). For -796T/G, there were significant differences in the genotype frequency between SAD and control subjects (P=0.009). This trend is still obvious in the subjects without APOEvarepsilon4 allele. The -796GG carriers might decrease the risk compared to the carriers with -796TG and TT genotypes (OR=0.602, 95%CI=0.393-0.932, P=0.022). No significant difference was detected either in genotype or in allele frequencies between SAD and control for -436C/T, even after APOEvarepsilon4 stratification. The haplotype -1216A/-796G may be a protective factor for SAD (OR=0.795, 95%CI=0.636-0.995, P=0.045). Our investigation suggests that -1216C/A and -796T/G are probably related to the development of SAD.
authors.affiliation: Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Key Neurodegenerative Laboratory of Ministry of Education of the People's Republic of China, 45 Changchun Street, Beijing 100053, PR China.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Ma
authors.forename: Di
authors.initials: D
authors.lastname: Han
authors.forename: Xiumei
authors.initials: X
authors.lastname: Zuo
authors.forename: Fen
authors.initials: F
authors.lastname: Wang
authors.forename: Jianping
authors.initials: J
authors.lastname: Jia
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics; D044466:Asian People / Q000235:genetics; D002353:Carrier State; D002681:China; D017931:DNA Primers; D005787:Gene Frequency; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012016:Reference Values
chemical_list: D053327:Apolipoprotein E4; D017931:DNA Primers; D008562:Membrane Glycoproteins; C413604:nicastrin protein; D053829:Amyloid Precursor Protein Secretases