The CC chemokine receptor 5 (CCR5) is a chemokine receptor which is widely expressed in several immune cells involved in the inflammatory responses. Previous published studies revealed the relation of the CCR5 gene (CCR5-delta32) with the risk of HIV-1 infection, but the results are debatable and inconclusive. Here by meta-analysis, we have systematically evaluated the relation between the CCR5-delta32 polymorphism and the risk of HIV-1 infection. A comprehensive search in PubMed, EMBASE, CNKI, Cochrane Library, and WanFang database was performed up to April 15, 2018. The pooled odds ratio (ORs) along with its 95% credible interval (95%CI) was used to evaluate the relation between the CCR5-delta32 polymorphism and HIV-1 infection risk. The study included 24 case-control studies involving 4,786 HIV-1 infection patients and 6,283 controls. Compared with the wild-type homozygous genotypes, the results showed that the CCR5-delta32 heterozygotes (OR=1.16, 95%CI=1.02-1.32) had an increased susceptibility to HIV-1 and the delta32 homozygous (OR=0.25, 95%CI=0.09-0.68) had significantly reduced the susceptibility to HIV-1 for healthy controls. Moreover, we have found the delta32 allele carriers (OR=0.71, 95%CI=0.54-0.94) had significantly cut down the HIV-1 infection susceptibility when using exposed uninfected (EU) as controls. We also conducted the stratified analysis by ethnicity, and there significant association was detected in Caucasian in delta32 allele carrier genotype. To summarize, our meta-analysis suggests that the CCR5-delta32 homozygous genotype (delta32/delta32) confer possible protection against HIV-1, especially the exposed uninfected groups.

Objectives: This study aims to investigate whether variations in LIPC, CETP, ABCA1 and LPL, which are involved in high/density lipoprotein (HDL) metabolism, are associated with advanced age-related macular degeneration (AMD) in the Chinese population. Design and Methods: A total of 119 Chinese patients with advanced AMD and 99 control individuals were recruited. Genomic DNA was extracted from peripheral blood leukocytes. Genotypes of seven single nucleotide polymorphisms (SNPs) including rs1061170 and rs1410996 in CFH, rs10490924 in HTRA1, rs10468017 in LIPC, rs3764261 in CETP, rs1883025 in ABCA1 and rs12678919 near LPL were determined by polymerase chain reaction (PCR) followed by allele-specific restriction enzyme digestion or SNaPshot. Unconditional logistic regression analyses were performed to generate a risk predictive model. Results: We observed the frequency of allele A of rs3764261 in CETP to be significantly lower in advanced AMD after Bonferroni correction (15.5% in patients with AMD and 20.7% in controls; OR=0.49, 95% CI: 0.29-0.85; p = 0.011). Furthermore, we found that it was also associated with reduced risk of both unilateral AMD (OR = 0.52, 95% CI: 0.28-0.98; p = 0.043) and bilateral AMD (OR = 0.45, 95% CI: 0.22-0.91; p = 0.026). Rs10468017 in LIPC, rs12678919 near LPL and rs1883025 in ABCA1 were not found to be associated with advanced AMD (all p>0.05). Conclusion: Our data suggested that the allele A in rs3764261 in CETP gene may be associated with a decreased risk of advanced AMD in Chinese population.

Objectives: This study aims to investigate whether variations in RAD51, B3GALTL, TNFRSF10A and REST-C4ORF14-POLR2B-IGFBP7 are associated with advanced forms of age-related macular degeneration (AMD) in Chinese population.Design and methods: A total of 119 Chinese patients with AMD and 99 control individuals were recruited. Genomic DNA was extracted from peripheral blood leukocytes. Seven single nucleotide polymorphisms (SNPs) from CFH, HTRA1, RAD51, B3GALTL, TNFRSF10A and REST-C4ORF14-POLR2B-IGFBP7 were genotyped by polymerase chain reaction (PCR) followed by allele-specific restriction enzyme digestion or SNaPshot.Results: Rs10483810 in RAD51 was significantly associated with advanced AMD (P = 0.045). Compared with the wild-type genotype GG, the odds ratio for the risk of advanced AMD was 4.92 (95% confidence interval: 1.04-23.36) for the heterozygous TG genotype. Moreover, the GT genotype at rs10483810 confers significantly increased risk of bilateral AMD compared to unilateral AMD (OR = 12.04, 95% CI: 2.50-57.69, P = 0.002). R513278062 in TNFRSF10A, rs1713985 in REST-C4ORF14-POLR2B-IGFBP7 and rs9542236 in B3GALTL were not found to be associated with AMD (all P>0.05).Conclusion: Our data suggested that the risk allele T of rs10483810 in RAD51 gene is associated with an increased risk of advanced AMD, especially bilateral AMD, in Chinese population. (C) 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Optic nerve degeneration caused by glaucoma is a leading cause of blindness worldwide. Patients affected by the normal-pressure form of glaucoma are more likely to harbor risk alleles for glaucoma-related optic nerve disease. We have performed a meta-analysis of two independent genome-wide association studies for primary open angle glaucoma (POAG) followed by a normal-pressure glaucoma (NPG, defined by intraocular pressure (IOP) less than 22 mmHg) subgroup analysis. The single-nucleotide polymorphisms that showed the most significant associations were tested for association with a second form of glaucoma, exfoliation-syndrome glaucoma. The overall meta-analysis of the GLAUGEN and NEIGHBOR dataset results (3,146 cases and 3,487 controls) identified significant associations between two loci and POAG: the CDKN2BAS region on 9p21 (rs2157719 [G], OR = 0.69 [95%CI 0.63-0.75], p = 1.86 x 10(-18)), and the SIX1/SIX6 region on chromosome 14q23 (rs10483727 [A], OR = 1.32 [95%CI 1.21-1.43], p = 3.87 x 10(-11)). In sub-group analysis two loci were significantly associated with NPG: 9p21 containing the CDKN2BAS gene (rs2157719 [G], OR = 0.58 [95% Cl 0.50-0.67], p = 1.17 x 10(-12)) and a probable regulatory region on 8q22 (rs284489 [G], OR = 0.62 [95% Cl 0.53-0.72], p = 8.88 x 10(-10)). Both NPG loci were also nominally associated with a second type of glaucoma, exfoliation syndrome glaucoma (rs2157719 [G], OR = 0.59 [95% Cl 0.41-0.87], p = 0.004 and rs284489 [G], OR = 0.76 [95% Cl 0.54-1.06], p = 0.021), suggesting that these loci might contribute more generally to optic nerve degeneration in glaucoma. Because both loci influence transforming growth factor beta (TGF-beta) signaling, we performed a genomic pathway analysis that showed an association between the TGF-beta pathway and NPG (permuted p = 0.009). These results suggest that neuro-protective therapies targeting TGFbeta signaling could be effective for multiple forms of glaucoma.

Transgene silencing is one of two major obstacles in both basic biomedical research for transgene and clinical practice of gene therapy. Based on the model of HT1080 cell clones, which transduced single copy of retroviral vector MGPN2, the mechanism of transgene silencing was explored in this investigation by a serial molecular techniques. In the HT1080 cell clone that absence of GFP protein synthesized, no significant aberration of epigenetic modification was detected, but the transcript size and the sequence changed that resulted in the reading frame shift. In addition to chromosomal position effect leading to transgene silencing, the transcript reading frame shift associated with retroviral vector rearrangements could induce complete silencing of transgene.