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The higher risks for AEs and mortality may offset the efficacy of atypical antipsychotics for treatment of dementia. Efficacy, safety, and tolerability thus should be carefully considered against clinical need.
Tumour necrosis factor-alpha (TNF-alpha), an important proinflammatory cytokine, exerts a variety of physiological and pathogenic effects that lead to tissue destruction. Studies on the association of TNF-alpha genetic polymorphisms with systemic lupus erythematosus (SLE) have yielded inconclusive results. We investigated the association of TNF-alpha genetic polymorphisms (-1031T/C, -863C/A, -857T/C, -308A/G and +489A/G) with SLE in Taiwanese patients and controls. Our results indicate that 1) the frequency of the A-allele at -863 position was significantly higher in SLE patients (odds ratio = 1.46; 95% CI = 1.02-2.08); 2) the frequency of the A-allele at +489 position was significantly higher in SLE patients (odds ratio = 1.79; 95% CI = 1.21-2.65); 3) the AA or GA genotype frequencies at +489 position were significantly increased in SLE patients (AA genotype: odds ratio = 11.20; 95% CI = 1.36-92.55; GA genotype: odds ratio = 1.63; 95% CI = 1.03-2.58); 4) no significant association of TNF-alpha haplotypic distributions was observed, except for the haplotypes TCCGA, CACGA and CCCGG; and 5) the genotype frequency of the polymorphisms at -1031 was significantly different in patients with antinuclear antibodies (P = 0.022). The allele and genotype frequencies of the polymorphisms at -863 were not significantly different. The genotype frequency of the polymorphisms at -857 was significantly different in patients with haematological disorder (P = 0.025). The frequency of A allele of the polymorphisms at -308 was significantly increased in patients with malar rash (P = 0.033), discoid rash (P = 0.023), photosensitivity (P = 0.037), oral ulcers (P = 0.002) and serositis (P = 0.029). The genotype frequency of the polymorphisms at +489 was significantly different in patients with discoid rash and photosensitivity (data not shown; discoid rash, P = 0.031; photosensitivity, P = 0.044). These results suggest that TNF-alpha genetic polymorphisms contribute to SLE susceptibility in the Taiwanese population.
Neurotensin (NT) is a 13-amino acid multifunctional neuropeptide. Previous studies have demonstrated the roles of NT and its high-affinity receptor 1 (NTR1) in genetically mediated differential sensitivities to alcohol. However, no studies have investigated the association between NTR1 gene single-nucleotide polymorphisms (SNPs) and alcohol dependence (AD). We therefore examined this link. We genotyped three SNPs (rs6090453C/G, rs6011914C/G, and rs2427422A/G) of NTR1 gene in 127 AD patients and 131 healthy controls drawn from Han Chinese males. Allele and genotype frequencies were compared, and linkage disequilibrium and haplotype analysis were performed. For rs6011914C/G, the frequencies of GG genotypes in AD patients showed an increased trend compared with controls (p = 0.057), and the ratio of GG/(CG + CC) for dominant model in AD patients was significantly higher (p = 0.024). For rs2427422A/G, both the frequencies of G alleles and GG genotypes and the ratio of GG/(AG + AA) for dominant model in AD patients were significantly higher compared with controls (p = 0.003, 0.006, 0.002, respectively). There was no significant difference in the frequencies of alleles, genotypes, and dominant or recessive model for rs6090453C/G (all p > 0.05). There were three pairs of SNP linkage disequilibriums, and the haplotype frequencies differed significantly between patients and controls for the CCA (p = 0.005, less frequent in the patients) and CCG (p = 0.002, more frequent in the patients) haplotypes. The current study supported an association between NTR1 gene variants and AD in the Han Chinese population.
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