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Purpose To identify novel susceptibility loci for high myopia. Design Genome-wide association study (GWAS) followed by replication and meta-analysis. Participants A total of 14 096 samples from East and Southeast Asian populations (2549 patients with high myopia and 11 547 healthy controls). Methods We performed a GWAS in 3269 Japanese individuals (1668 with high myopia and 1601 control participants), followed by replication analysis in a total of 10 827 additional samples (881 with high myopia and 9946 control participants) from Japan, Singapore, and Taiwan. To confirm the biological role of the identified loci in the pathogenesis of high myopia, we performed functional annotation and Gene Ontology (GO) analyses. Main Outcome Measures We evaluated the association of single nucleotide polymorphisms with high myopia and GO terms enriched among genes identified in the current study. Results We identified 9 loci with genome-wide significance (P Conclusions The current study identified 6 novel loci associated with high myopia and demonstrated an important role of the nervous system in the disease pathogenesis. Our findings give new insight into the genetic factors underlying myopia, including high myopia, by connecting previous findings and allowing for a clarified interpretation of the cause and pathophysiologic features of myopia at the molecular level.

Action of Toll-like receptors (TLRs) is deeply associated with defense mechanisms of the innate and adaptive immune responses to microbial pathogens. There have been reports of genetic polymorphisms within the TLR7 gene being closely related to a variety of inflammatory and infectious diseases. Behçet's disease (BD) is an autoinflammatory disease, and the pathogenesis has yet to be fully discovered. We investigated whether polymorphisms of Toll-like receptor 7 (TLR7) are associated with BD by analyzing the frequency of eight single nucleotide polymorphisms (SNPs) within 200 Japanese BD patients and 102 randomized controls. We genotyped nine SNPs in the TLR7 gene and assessed the allele/genotype diversity between cases and controls for all SNPs. In all eight SNPs, statistically significant differences were not observed between cases and controls.

Single HIV-1 subtype DNA vaccine is unlikely to provide reactive protection across a wide range of HIV strains since the HIV virus changes the antigenic sites, particularly, in env gene. To overcome these issues, we constructed a multivalent poly-epitope DNA vaccine. A polygenic DNA vaccine encoding 20 antigenic epitopes from the HIV-1 Env, Gag, and Pol proteins of several clades was constructed using humanized and optimized codons and it was named here hDNA vaccine. In mice, this hDNA vaccine stimulated the following strong (1) antigen-specific serum antibody (Ab) responses, (2) delayed-type hypersensitivity, (3) the activation of IFN-gamma secretion cells targeting gp120 and synthetic antigenic peptides, in addition (4) a significant level of several peptide specific cytotoxic T lymphocytes (CTL) responses. Challenged with modified vaccinia viruses vPE16 and vP1206 expressing HIV-1 env and gag.pol genes, respectively, demonstrated the viral titers in the ovary of the mice vaccinated with hDNA significantly less compared to the unvaccinated mice. Thus, the use of polygene DNA vaccine appears to induce a high level of HIV-specific immune responses and is very effective against challenge with recombinant HIV-vaccinia viruses.

To clarify the prevalence of open-angle glaucoma (OAG) and its relationship to refraction among a Japanese population with a broad range of ages including children and adolescents, an 1-year epidemiological survey was conducted. The subjects of this study were 64,394 asymptomatic individuals who had attended the glasses and contact lens center in Yokohama, Japan from February 15, 1999 to February 14, 2000 and had been subjected to several optical examinations. The results of this study showed that the overall prevalence of OAG was 1.19% (1.14% for men, and 0.98% for women). Prevalence for children aged 6 to 14 of both sexes was approximately 0.5%. There were significant positive associations between the strength (diopter) of myopic refraction and OAG prevalence among all the examined subjects.

DNA vaccination is characterized by its preferential induction of the cytotoxic T cell lymphocyte (CTL) response and is expected to be a useful means of protection against viral infection. We examined the protective effect of an expression plasmid (pME18S-M) containing M1 and M2 genes of influenza A/PR/8/34. We detected the CTL activity by introducing these plasmids into BALB/c mice by either the intramuscular or the intranasal route. The influenza-specific antibody response was also induced, although its neutralizing effect against influenza virus was not observed. From 70 to 80% protection was observed in the mice immunized with the pME18S-M plasmid followed by lethal infection with influenza viruses of the A/WSN/33 and A/PR/8/34 strains, whereas all mice without the plasmid vaccination failed to survive. This protective activity was significantly weakened when the CD8(+) cells of these immunized mice were eliminated by several injections of anti-CD8 antibody. The protective activity was also weakened when anti-CD4 antibody was injected in the early phase of DNA vaccination. These data suggest that the pME18S-M plasmid is useful as a DNA vaccine for overcoming highly mutational influenza viruses.