A1166C polymorphism of the angiotensin II type 1 receptor gene contributes to hypertension susceptibility: evidence from a meta-analysis

<p>Background The angiotensin II type 1 receptor (AT1R) gene is a prime candidate for polymorphisms that could contribute to hypertension. A polymorphism in the 3’ untranslated region, leading to the transversion of adenine to cytosine at position 1166, has been the most-studied variant. However, the results have been inconsistent, and we therefore performed a meta-analysis to evaluate the association of this polymorphism with hypertension.</p> <p>Methods We conducted an extended a computer-based literature search of PubMed and Web of Knowledge up to November 30, 2015. The extracted data were analysed statistically, and pooled odds ratios with 95% confidence intervals were calculated to assess the strengths of associations using Review Manager software (version 5.2).</p> <p>Results After removing 5 studies that were not consistent with the Hardy-Weinberg equilibrium, we finally collected 41 case–control studies involving 11,837 cases and 11,020 controls to evaluate the association between AT1R polymorphisms and hypertension. We found that the risk of hypertension was higher for allele C than for allele A under the codominant model, significantly higher for genotype CC + AC than for genotype AA under the dominant model, and significantly higher for genotype CC + AC in Caucasians.</p> <p>Conclusion This meta-analysis suggests that the AT1R 1166 CC + AC genotype consistently confers susceptibility to hypertension and that early preventive measures should be applied in clinical settings according to patient genotypes.</p

Data_Sheet_1_SbbR/SbbA, an Important ArpA/AfsA-Like System, Regulates Milbemycin Production in Streptomyces bingchenggensis.docx

<p>Milbemycins, a group of 16-membered macrolide antibiotics, are used widely as insecticides and anthelmintics. Previously, a limited understanding of the transcriptional regulation of milbemycin biosynthesis has hampered efforts to enhance antibiotic production by engineering of regulatory genes. Here, a novel ArpA/AfsA-type system, SbbR/SbbA (SBI_08928/SBI_08929), has been identified to be involved in regulating milbemycin biosynthesis in the industrial strain S. bingchenggensis BC04. Inactivation of sbbR in BC04 resulted in markedly decreased production of milbemycin, while deletion of sbbA enhanced milbemycin production. Electrophoresis mobility shift assays (EMSAs) and DNase I footprinting studies showed that SbbR has a specific DNA-binding activity for the promoters of milR (the cluster-situated activator gene for milbemycin production) and the bidirectionally organized genes sbbR and sbbA. Transcriptional analysis suggested that SbbR directly activates the transcription of milR, while represses its own transcription and that of sbbA. Moreover, 11 novel targets of SbbR were additionally found, including seven regulatory genes located in secondary metabolite biosynthetic gene clusters (e.g., sbi_08420, sbi_08432, sbi_09158, sbi_00827, sbi_01376, sbi_09325, and sig24_sbh) and four well-known global regulatory genes (e.g., glnR_sbh, wblA_sbh, atrA_sbh, and mtrA/B_sbh). These data suggest that SbbR is not only a direct activator of milbemycin production, but also a pleiotropic regulator that controls the expression of other cluster-situated regulatory genes and global regulatory genes. Overall, this study reveals the upper-layer regulatory system that controls milbemycin biosynthesis, which will not only expand our understanding of the complex regulation in milbemycin biosynthesis, but also provide a basis for an approach to improve milbemycin production via genetic manipulation of SbbR/SbbA system.</p