The COL1A1 gene and high myopia susceptibility in Japanese.

The collagen type Iota alpha Iota (COL1A1) gene encodes the extracellular matrix component, collagen, and resides in candidate MYP5 for high myopia on the chromosome 17q22-q23.3. This locus has recently been implicated in playing an important role in the pathogenesis of experimental myopia. We investigated the association of disruptions of COL1A1 gene with high myopia by analyzing the frequency of ten SNPs in a Japanese population of 330 subjects with high myopia of -9.25 D or less and 330 randomized controls without high myopia. Two SNPs (rs2075555 and rs2269336) were significantly associated with high myopia (P < 0.05, Pc < 0.1). Two different haplotype blocks in COL1A1 were observed by the pair-wise linkage disequilibrium between the SNPs. The frequency of GGC/GGC diplotype constructed by the three SNPs (rs2075555, rs2269336, rs1107946) was significantly high (OR = 1.6) and associated with high myopia (P = 0.028, Pc< 0.084). Together our results provide the first evidence for COL1A1 as a gene associated with high myopia.

Exclusion of transforming growth factor-beta1 as a candidate gene for myopia in the Japanese.

PURPOSE: To determine whether single-nucleotide polymorphisms (SNPs) within the transforming growth factor-beta1 (TGF-beta1) gene are associated with high myopia in Japanese. Previous studies have indicated that the gene expression products, regulators of the TGF-beta1 gene, are involved in high myopia. METHODS: Genomic DNA samples were obtained from 330 Japanese patients with high myopia and 330 Japanese controls without high myopia who were chosen at random. SNPs were genotyped by the TaqMan system, using primer extension and polymerase chain reaction amplification. RESULTS: Ten SNPs were identified in the high-myopia patients and controls, with four of the ten SNPs having nonsynonymous changes. However, no statistical differences in the SNPs were detected between the high-myopia cases and the controls. CONCLUSIONS: Sequence variants of the TGF-beta1 gene were not associated significantly with high myopia, and further studies are needed to identify which genes are responsible for high myopia.

A single nucleotide polymorphism analysis of the LAMA1 gene in Japanese patients with high myopia.

Although a myopia susceptibility gene has not yet been elucidated, ten candidate regions (MYP1-MYP10) have been associated with myopia by linkage analysis employing large pedigrees. We report herein on the results of our analysis pertaining to polymorphisms of LAMA1 (alpha subunit of laminin), a promising candidate gene for high myopia present in the MYP2 region of Japanese subjects with high myopia. Three hundred and thirty Japanese subjects with high myopia at a level of greater than -9.25 D and ethnically and sex matched 330 normal controls without high myopia was enrolled in this study. The thirteen SNPs located on the LAMA1 gene were analyzed using PCR and SNP-specific fluorogenic probes. Two of the SNPs were monomorphic and none of the 11 SNPs showed statistically significant association with high myopia in the Japanese population. There is no convincing evidence to prove a connection between nucleotide sequence variations in LAMA1 and high myopia. The pairwise linkage disequilibrium (LD) mapping disclosed a strong value (D' > 0.8) and narrow ranged block within these SNPs.

Lack of association with high myopia and the MYP2 locus in the Japanese population by high resolution microsatellite analysis on chromosome 18.

MYP2 was reported for a candidate locus associated with high grade myopia by linkage analysis, but no candidate gene has been detected. We report an association study in the Japanese population using 750 microsatellite markers on chromosome 18 that include MYP2 locus. 450 Japanese subjects with high myopia whose refractive error was greater than or equal to -9.25D in at least one eye and equal number of normal control subjects were recruited in this study. Three steps screening on the pooled DNA of patients and the pooled DNA of controls were performed in this study. A total of 722 microsatellite markers could be analyzed, and we obtained 4 positive markers. Then to avoid experimental errors and artifacts, we confirmed true allele frequency by individual genotyping using initial set of 450 patients and controls. Only marker D18S0301i showed statistically significance, and no marker showed statistically significance on the MYP2 locus. Near the marker D18S0301i, GALNT1 gene was located, but its relation to high myopia has remained to be identified.

Analysis of single nucleotide polymorphisms at 13 loci within the transforming growth factor-induced factor gene shows no association with high myopia in Japanese subjects.

A previous study in China first indicated that the transforming growth factor-induced factor (TGIF) is a probable candidate gene for high myopia. The purpose of our study was to investigate whether there are significant associations between high myopia and single nucleotide polymorphism (SNP) variants in the TGIF gene of Japanese subjects. Genomic DNA was collected from 330 Japanese subjects with high myopia and at a level refractive error was less than -9.25 Dsph and 330 randomized controls without high myopia. Thirteen SNPs were detected by polymerase chain reaction (PCR) and primer extension or by PCR and SNP-specific fluorogenic probes in all of the cases and controls. Thirteen SNPs were found within the TGIF genes of the cases and controls. Two of the SNPs were monomorphic and none of the 13 SNPs showed a significant result. The pairwise linkage disequilibrium (LD) mapping confirmed that these alleles have a comparatively strong LD index of >0.8 for D' and >0.4 for r(2). We found no statistical association between any of the 13 SNPs located on the TGIF gene and high myopia in Japanese subjects. Based on our study using Japanese subjects and the previous studies of TGIF gene polymorphism in Chinese and northern European subjects with myopia, there is no convincing evidence to prove a connection between nucleotide sequence variations in TGIF and high myopia.

Contact lens user statistics in Okada eye clinic.

PURPOSE: To investigate the relationships between contact lens wearers, their lens wear, and treatment to provide correct instructions for use. METHOD: A total of 55,056 consumers, who purchased contact lenses in the two institutions of Okada Eye Clinic in the 1-year period from April 1, 2002 to March 31, 2003, were analyzed with regard to age, sex, contact lens brands, treatments and lens-solution combinations purchased, and patterns of wear. RESULTS: The 2-week frequent-replacement soft contact lenses were the most popular type of contact lens, and most wearers of these lenses were those in their 20s. Saline solution was the treatment purchased most often with conventional soft contact lenses. Hard contact lens wearers tended to buy treatments of the same brand as their hard contact lenses. Hydrogen peroxide was the most purchased product with the 2-week frequent-replacement soft contact lenses and multipurpose treatment the next, especially with consumers in their 20s. There were no significant sex gaps. CONCLUSIONS: The survey was conducted on a wide age range of more than 50,000 people and can be assumed to accurately reflect the tendencies of contact lens wearers in Japan. The results clearly show the actual use of contact lenses and treatments of each age group and will be useful in instructing wearers to the correct use of their treatments.

An investigation of the actual conditions of use of daily-disposable soft contact lenses and two-week disposable soft contact lenses.

PURPOSE: To investigate whether daily-disposable and 2-week disposable soft contact lenses are being used correctly. METHODS: The number of purchases made and brands selected by the 44,566 consumers who purchased daily-disposable and 2-week disposable soft contact lenses in Okada Eye Clinic institutions between April 1, 2002 and November 1, 2002 were monitored. From the 7,759 respondents to a survey conducted in the clinic between November 1, 2002 and March 31, 2003, the number of purchases made and brands selected by the 1,584 respondents, whose sales records could be traced, were analyzed in further detail. RESULTS: The total number of consumers purchasing daily-disposable soft contact lenses was 14,909, and their annual average purchase was 10.56 boxes. Most purchases were of two boxes followed by purchases of four and then six. Only 6.4% of consumers purchased 24 boxes at a time. Consumers purchasing four or fewer boxes at a time accounted for 37.8%. A total of 25,705 consumers purchased 2-week disposable soft contact lenses, with an annual average purchase of 6.37 boxes per consumer. Nineteen percent of the consumers purchased eight boxes of 2-week disposable soft contact lenses per year. Most consumers tended to purchase their contact lenses in even numbers for daily-disposable and 2-week disposable soft contact lenses. Johnson & Johnson Vision Care (Jacksonville, FL) was the most popular manufacturer. According to the survey, 86.6% of the 2-week disposable soft contact lens wearers followed instructions correctly, whereas 13.4% did not. That is, they exceeded the instructed 14 days of wear. CONCLUSIONS: Annual average purchases of daily-disposable and 2-week disposable soft contact lenses tended to be in even numbers and showed differences in their sales depending on contact lens brands. The results obtained from the survey and the actual sales records correlated.

Expression of tumor suppressor gene product p14ARF in endometrioid adenocarcinoma of the uterine corpus.

p14 activates p53 by inhibiting MDM2 expression and arrests the cell cycle in G1 and G2/M. Abnormal p14 expression has been reported in various human cancers. This study investigated p14 expression in endometrioid adenocarcinoma of the uterine corpus in an attempt to clarify its correlation with other cell cycle-regulators and clinicopathologic parameters. The specimen studied consisted of 124 endometrioid adenocarcinomas, 20 normal endometria, and 20 endometrial hyperplasias. Immunohistochemical staining of formalin-fixed and paraffin-embedded tissues was performed using a Catalyzed Signal Amplification System. Cells with >5% positive staining were classified as positive for p14. A staining score of 1 was adopted when the percentage of positive nuclei was <5%, a score of 2 when it was 5 to 50%, and a score of 3 when it was >50%. In normal endometrium, the frequency of positive staining in the proliferative phase and secretory phase was 50% (4/8) and 58.3% (7/12), with staining scores of 1.8+/-0.9 and 1.6+/-0.5, respectively. The frequency of staining in simple hyperplasia (SH), complex hyperplasia (CH), and complex atypical hyperplasia (CAH) was 88.9% (8/9), 25% (1/4), and 42.9% (3/7), respectively; the staining scores were 1.9+/-0.3, 1.3+/-0.5, and 1.4+/-0.5, respectively. Among endometrioid adenocarcinomas, the frequency of staining of well-differentiated (G1), moderately differentiated (G2), and poorly differentiated (G3) adenocarcinomas was 69% (49/71), 64% (16/25), and 42.9% (12/28) respectively, with staining scores of 2.1+/-0.8, 2+/-0.9, and 1.8+/-1, respectively. Thus expression levels of p14 were higher in G1 tumors than in normal endometria or endometrial hyperplasias, and the frequency of its staining in endometrioid carcinomas was inversely correlated with histologic grade. The staining score for endometrioid adenocarcinomas also was inversely correlated with the labeling index (LI) of Ki-67, but not with that of cyclin A, cyclin D1, cyclin E, cdk2, p27, p53, or other clinicopathologic parameters. In conclusion, p14 expression correlated with histologic grade and Ki-67, but not other prognostic factors in endometrioid adenocarcinoma. Long-term follow-up studies are needed to analyze the significance of p14 expression in these tumors.