ABSTRACT
BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease with a higher prevalence in women. Expression of estrogen receptor 1 (ESR1) gene has been identified throughout the brain. Owing to the putative neuroprotective effects of estrogen, estrogen receptor gene is a potential candidate modulating the development of AD. Preliminary associations between two polymorphisms of ESR1 (PvuII and XbaI) gene and AD have been reported. METHODS: In this study, 16 single nucleotide polymorphisms (SNPs) of the ESR1 gene (including four commonly studied ESR1 SNPs and 12 other tagging SNPs selected from the HapMap database) were investigated to further evaluate the association between ESR1 polymorphisms and the risk of AD in the Chinese population. RESULTS: A total of 233 Chinese AD patients and 245 age-matched elderly control subjects were recruited. Genetic associations were analyzed by chi-square test and interaction effect was analysed by logistic regression analysis. Five SNPs (clustered between intron 3 and intron 7) were associated with the risk of AD (p-value ranges from 0.001 to 0.035); another two SNPs (located on exon 2 and intron 2) were shown to modulate the age-at-onset (AAO) in AD (p-value = 0.036 and 0.011). CONCLUSIONS: ESR1 gene polymorphisms may be associated with the AAO in AD. The present results provided information for possible associations between certain polymorphisms of ESR1 gene and the risk of AD.
Subject(s)
Alleles , Alzheimer Disease/genetics , Asian People/genetics , Cross-Cultural Comparison , Estrogen Receptor alpha/genetics , Polymorphism, Single Nucleotide/genetics , Age of Onset , Aged , Aged, 80 and over , Alzheimer Disease/ethnology , Female , Genetic Predisposition to Disease/genetics , Genotype , Haplotypes/genetics , Hong Kong , Humans , Introns/genetics , Linkage Disequilibrium , Male , Risk , Risk Factors , White People/geneticsABSTRACT
Early growth response-1 (Egr-1) is expressed in human airways and found to modulate tumor necrosis factor, immunoglobulin E (IgE), airway responsiveness, and interleukin-13-induced inflammation in mice. We investigated the effects of Chinese-tagging single nucleotide polymorphisms (SNPs) of Egr-1 on asthma traits in 298 Chinese asthmatic children and 175 controls, and a replication community cohort of 191 controls. Tag SNP (-4071 A-->G) and three additional SNPs (-1427 C-->T, -151 C-->T and IVS1 -42 C-->T) were genotyped by restriction fragment length polymorphism (RFLP). Significant associations were found between plasma total IgE concentration and -4071 A-->G (p = 0.008) and IVS1 -42 C-->T (p = 0.027) in asthmatic patients. After Bonferroni correction, only -4071 A-->G showed significant association. Multivariate regression analysis confirmed this significant association with a standardized coefficient beta of 0.156 (95% CI: 0.046-0.317; p = 0.009) in asthmatics among the three SNPs with age and gender-adjusted. In -4071 A-->G, IgE(log) was significantly higher in patients with the GG genotype than the AA genotype (p = 0.009). In addition, -4071 A-->G was significantly associated with atopy (p = 0.016) and high total IgE concentration (p = 0.030) among asthmatics. Patients with the G allele had a 3.5-fold risk of having atopy and a 2.0-fold risk of having high total IgE concentration than those homozygous for the A allele. This is the first report to show significant association of Egr-1 polymorphisms with plasma total IgE and atopy in asthmatics. It may help to explore the pharmacogenetics of Egr-1 inhibitors.
