The frequency of transforming growth factor-TGF-B gene polymorphisms in a normal southern Iranian population

Several single nucleotide polymorphisms (SNPs) of the transforming growth factor-β1 gene (TGFB1) have been reported. Determination of TGFB1 SNPs allele frequencies in different ethnic groups is useful for both population genetic analyses and association studies with immunological diseases. In this study, five SNPs of TGFB1 were determined in 325 individuals from a normal southern Iranian population using polymerase chain reaction-restriction fragment length polymorphism method. This population was in Hardy-Weinberg equilibrium for these SNPs. Of the 12 constructed haplotypes, GTCGC and GCTGC were the most frequent in the normal southern Iranian population. Comparison of genotype and allele frequencies of TGFB SNPs between Iranian and other populations (meta-analysis) showed significant differences, and in this case the southern Iranian population seems genetically similar to Caucasoid populations. However, neighbour-joining tree using Nei's genetic distances based on TGF-β1 allele frequencies showed that southern Iranians are genetically far from people from the USA, Germany, UK, Denmark and the Czech Republic. In conclusion, this is the first report of the distribution of TGFB1 SNPs in an Iranian population and the results of this investigation may provide useful information for both population genetic and disease studies. © 2008 The Authors

Interleukin-6 polymorphisms modify the risk of periodontitis: a systematic review and meta-analysis

Objective: To clarify the association of IL-6 polymorphisms and periodontitis, a meta-analysis of case-control studies and a systemic review were conducted. Material and methods: We performed a literature search using PubMed and Medline database to May 2009, with no restrictions. We also reviewed references from all retrieved articles. Six case-control studies involving 1 093 periodontitis cases and 574 controls were selected for meta-analysis to assess the purported associations between IL-6 polymorphisms and the risk of periodontitis. IL-6 −174 G/C and −572 C/G polymorphisms were included in the present meta-analysis, and the association between IL-6 −6331 T/C polymorphism and the risk of periodontitis was adequately reviewed as well. Results and conclusion: The present meta-analysis indicates that the IL-6 −174 G allele could not modify the risk of chronic periodontitis, but increased the risk of aggressive periodontitis. And −572 C/G polymorphism is associated with the pathogenesis of periodontitis, including chronic periodontitis or aggressive periodontitis

<i>De Novo</i> Mutations in Protein Kinase Genes <i>CAMK2A</i> and <i>CAMK2B</i> Cause Intellectual Disability

Calcium/calmodulin-dependent protein kinase II (CAMK2) is one of the first proteins shown to be essential for normal learning and synaptic plasticity in mice, but its requirement for human brain development has not yet been established. Through a multi-center collaborative study based on a whole-exome sequencing approach, we identified 19 exceedingly rare de novo CAMK2A or CAMK2B variants in 24 unrelated individuals with intellectual disability. Variants were assessed for their effect on CAMK2 function and on neuronal migration. For both CAMK2A and CAMK2B, we identified mutations that decreased or increased CAMK2 auto-phosphorylation at Thr286/Thr287. We further found that all mutations affecting auto-phosphorylation also affected neuronal migration, highlighting the importance of tightly regulated CAMK2 auto-phosphorylation in neuronal function and neurodevelopment. Our data establish the importance of CAMK2A and CAMK2B and their auto-phosphorylation in human brain function and expand the phenotypic spectrum of the disorders caused by variants in key players of the glutamatergic signaling pathwa