Meta-Analysis of Cytokine and Chemokine Genes in Schizophrenia.

INTRODUCTION: Immune system genes, including cytokines, are associated with schizophrenia risk. Polymorphisms in cytokine genes may also impact on blood levels of cytokines, which are altered in patients with schizophrenia. We performed a meta-analysis of case-control studies of cytokine and chemokine genes in schizophrenia that have not been considered in previous quantitative reviews. METHODS: We identified articles by systematic searches of PubMed, PsycInfo, and ISI, and the reference lists of identified studies. For each cytokine or chemokine polymorphism, we performed an allele- and genotype-wise meta-analysis, using a random effects model. RESULTS: Twenty-one independent studies met the inclusion criteria, comprising polymorphisms for the IL1B, IL2, IL4, IL6, sIL6R, MCP1, and TGFB1 genes. For IL6, the A allele (OR=0.95, 95% CI 0.91-0.99) and AA genotype (OR=0.65, 95% CI 0.50-0.85) for the rs1800795 polymorphism, and for sIL6R, the A allele (OR=0.96 95%, CI 0.92-1.00) and AA genotype (OR=0.72, 95% CI 0.55-0.94) the rs8192284 polymorphism were associated with significantly decreased schizophrenia risk. In the genotype-wise analysis for IL1B, homozygosity for either allele (AA: OR=1.91, 95% CI 1.60-2.27; and GG: OR=0.40, 95% CI 0.33-0.49) of the rs1143627 polymorphism was also significantly associated with schizophrenia risk. CONCLUSIONS: Associations between polymorphisms for the IL1B, IL6, and sIL6R genes and schizophrenia risk complement and extend previous findings regarding immune dysfunction in this disorder, including genome-wide association studies. Future studies of cytokine expression in schizophrenia should consider the effect of these polymorphisms. The finding of potential "protective" alleles may also be relevant for at-risk populations.

Synthesis and characterization of gold(III) complexes possessing 2,9-dialkylphenanthroline ligands: to bind or not to bind?

In an effort to discover potential alternatives to the anti-cancer drug cisplatin, the synthesis of gold(III) polypyridyl coordination complexes was pursued. Specifically, this report describes the synthesis and characterization of a series of 2,9-dialkyl-1,10-phenanthroline (Rphen) gold(III) coordination complexes (R = n-butyl, sec-butyl, and tert-butyl). Due to the steric hindrance imparted by the alkyl substituents, these ligands do not react with HAuCl4 to form square-planar gold(III) dichloride complex ions, as is the case with 1,10-phenanthroline, but instead form salts comprised of [AuCl(4)](-) anions and protonated 2,9-dialkylphenanthroline cations (compounds 1 and 2). In an effort to facilitate direct binding between the substituted phenanthroline and the gold(iii) metal center, reactions were carried out between the ligand and NaAuCl4 in the presence of a Ag(I) salt. The precipitation of one equivalent of AgCl afforded the formation of neutral, distorted square-pyramidal gold(iii) trichloride complexes (compounds 3 and 4). Primary or secondary substitutions at the alpha carbon of the alkyl substituent allow direct metal-ligand coordination, whereas a tertiary substituent inhibits chelation and results only in the formation of a salt comprised of a protonated phenanthroline cation and a [AuCl2]- anion (compound 5). Compounds 1-4 have been characterized by 1H NMR, UV/vis, IR spectroscopy, and X-ray crystallography.