Polymorphism of beta-adrenergic receptors and susceptibility to open-angle glaucoma.

PURPOSE: The human trabecular meshwork and ciliary body, which express beta-adrenergic receptors (ADRB1 and ADRB2), control aqueous humor dynamics. We investigated associations of ADRB polymorphisms with open-angle glaucoma (OAG), because ADRB gene polymorphisms alter receptor function. METHODS: We studied 240 Japanese controls and 505 Japanese OAG patients including 211 with primary open-angle glaucoma (POAG), and 294 with normal-tension glaucoma (NTG). Associations of four polymorphisms (Ser49Gly and Arg389Gly in the ADRB1 gene; Arg16Gly and Gln27Glu in the ADRB2 gene) were compared between patients and controls. Age, intraocular pressure (IOP), and visual field defects at diagnosis were examined for associations with polymorphisms. RESULTS: The Arg389Gly polymorphism in the ADRB1 gene showed significantly different allele and genotype frequencies in patients with NTG than in controls (p = 0.004 and 0.006, respectively). Other polymorphisms did not show a significant frequency difference. In POAG patients, carriers of Gly16 in the ADRB2 gene were significantly younger at diagnosis than noncarriers (p<0.001). The IOP at diagnosis was significantly higher in OAG patients carrying 27Glu in the ADRB2 gene than in patients without this allele (p<0.001). Clinical characteristics of OAG patients did not differ significantly in relation to other polymorphisms. CONCLUSIONS: Certain polymorphisms of the ADRB1 and ADRB2 genes influence the pathophysiology of OAG in Japanese patients.

Mitochondrial DNA mutations with Leber's hereditary optic neuropathy in Japanese patients with open-angle glaucoma.

PURPOSE: Abnormal optic disc excavations are found in patients with Leber's hereditary optic neuropathy (LHON). The purpose of this study was to determine whether heteroplasmy for the major three LHON mutations or for the rare LHON mutations are risk factors for open-angle glaucoma. METHODS: Blood samples from 835 Japanese subjects were screened with the Invader assay for ten LHON-associated mutations: three major mutations (G3460A, G11778A, T14484C) and seven rare mutations (T9101C, G9804A, C14482A, C14482G, G14459A, T14498C, and A14510G). Of the 835 subjects, 241 were patients with primary open-angle glaucoma (POAG), 310 were patients with normal-tension glaucoma (NTG), and 284 were healthy controls. RESULTS: Five POAG patients and three NTG patients had one of five mutations, C9099A, T9101G, T9101C, G9804A, or G11778A, but none of these patients had LHON. The C9099A (Ile191Met) and T9101G (Ile192Ser) mutations were novel and identified within the probes by lack of signal in the assay. Two patients with the G11778A mutation showed heteroplasmy, with 15% mutant mtDNA in the male patient and 80% in the female patient. The remaining LHON-associated mutations were not detected in any of the subjects. A case-control study did not show a significant difference (P = 0.099): eight potentially disease-associated variants in 551 patients versus zero variants in the 284 controls. CONCLUSIONS: Rare LHON-associated mitochondrial DNA mutations were found in Japanese patients with open-angle glaucoma (OAG). However, whether mitochondrial DNA mutations are risk factors for OAG is still open to question.

Paraoxonase 1 gene polymorphisms influence clinical features of open-angle glaucoma.

BACKGROUND: The purpose of this study was to determine whether genetic polymorphisms affecting high-density lipoprotein (HDL)-associated antioxidant enzymes were associated with open-angle glaucoma (OAG). The rationale for this study was that the modification of low-density lipoprotein (LDL) by HDL prevents oxidative modification which can then cause dysfunction of endothelial cells. METHODS: We studied 284 normal Japanese controls and 555 Japanese patients with OAG, including primary open-angle glaucoma (POAG) and normal-tension glaucoma (NTG). The possible associations of polymorphisms of PON1/L55M, PON1/Q192R, PON2/S311C, and PAF-AH/V279F with OAG were investigated. We compared the genotype distributions and allele frequency in controls and patient groups. The age at diagnosis, intraocular pressure (IOP) at diagnosis, and visual field score at diagnosis were examined for association with polymorphisms. RESULTS: The distributions of genotypes and allele frequency for the four polymorphisms were not significantly different between any patient group and controls. In NTG patients, 55M carriers of the PON1 gene were significantly older at diagnosis than 55M non-carriers (P=0.001). The IOP at diagnosis was significantly higher in glaucoma patients carrying 192R in the PON1 gene than in patients not carrying 192R (P=0.006). No significant differences were seen in clinical characteristics of OAG patients in relation to other polymorphisms. CONCLUSION: PON1 gene polymorphisms may influence the features of Japanese patients with OAG.

Genetic variants of TP53 and EPHX1 in Leber's hereditary optic neuropathy and their relationship to age at onset.

PURPOSE: To determine whether genetic polymorphisms of the genes for oxidative stress and apoptosis cause the clinical variability in patients with Leber's hereditary optic neuropathy (LHON). METHODS: Eighty-seven unrelated Japanese LHON patients carrying the 11778 mitochondrial mutation were studied at the Keio University Hospital. Their mean age (+/-SD) was 25.0 +/- 13.0 years with a range 3 to 65 years. Eleven polymorphisms in nine genes were studied: seven genes related to oxidative stress (SOD2, GSTT1, GSTM1, EPHX1, NQO1, p22 PHOX, and NOS3), and two genes related to apoptosis (TP53 and CD95). Each genetic polymorphism was analyzed in relation to the age at onset and the final visual acuity. RESULTS: Among the oxidative stress-related polymorphisms, a significant association between Tyr113His in the EPHX1 gene and the age at onset of the disease was identified (P = 0.026). LHON patients who were homozygous for His113 developed the disease earlier than those without this genotype (21.9 vs. 27.9 years). Among the apoptosis-related polymorphisms, a significant association between Arg72Pro in the TP53 gene and the age at onset was identified (P = 0.007). LHON patients who were homozygous for Arg72 developed the disease earlier than those without this genotype (20.5 vs. 28.1 years). In addition, LHON patients with both genotypes developed the disease significantly earlier (17.5 years, P = 0.011). No associations were found between the final visual acuity and the genetic polymorphisms examined. CONCLUSION: Nuclear genetic polymorphisms related to oxidative stress or apoptosis may modify the age at onset of LHON.

Simple and inexpensive software designed for the evaluation of color.

PURPOSE: To report on new software that was specially designed to evaluate color. METHODS: Software development and observational case report. Each pixel on a computer screen is composed of three colors: red, green, and blue (RGB). Our software analyzes the intensity of each RGB component in a specific area chosen by the user. To test our software, we evaluated the color level of the irises of a subject, which became darker as a side effect of Xalatan (latanoprost; Pharmacia Corporation, Peapack, New Jersey) eyedrops. RESULT: We successfully expressed the level of the color of the iris by number. CONCLUSION: This software measures the color of a lesion and thereby provides an objective evaluation of color. The software we developed is downloadable, without cost, from http://www.isao.com.