Risk Of Primary Open-angle Glaucoma Research Articles

Glutathione S-transferase M1 polymorphism and primary open-angle glaucoma (POAG) in a Chinese population

Primary Open-Angle Glaucoma (POAG) is a leading cause of irreversible blinding disease. We conducted this case-control study to assess the association between GSTM1 null polymorphism and POAG risk in Chinese. Unrelated 323 adult-onset POAG patients and 295 control subjects were recruited. We found that patients carrying the GSTM1 null genotype had increased risk of POAG (OR=1.80, 95% CI 1.25-2.54, P=0.002). No statistically significantly association was found between GSTM1 polymorphism and smoking status. However, GSTM1 polymorphism was significantly associated with diabetes mellitus in patients. In conclusion, the GSTM1 polymorphism was significantly associated with the risk of POAG.

Association of Interleukin-1 gene clusters polymorphisms with primary open-angle glaucoma: a meta-analysis

BackgroundPrevious studies have associated the Interleukin-1 (IL-1) gene clusters polymorphisms with the risk of primary open-angle glaucoma (POAG). However, the results were not consistent. Here, we performed a meta-analysis to evaluate the role of IL-1 gene clusters polymorphisms in POAG susceptibility.MethodsPubMed, EMBASE and Cochrane Library (up to July 15, 2017) were searched by two independent investigators. All case-control studies investigating the association between single-nucleotide polymorphisms (SNPs) of IL-1 gene clusters and POAG risk were included. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for quantifying the strength of association that has been involved in at least two studies.ResultsFive studies on IL-1β rs16944 (c. -511C > T) (1053 cases and 986 controls), 4 studies on IL-1α rs1800587 (c. -889C > T) (822 cases and 714 controls), and 4 studies on IL-1β rs1143634 (c. +3953C > T) (798 cases and 730 controls) were included. The results suggest that all three SNPs were not associated with POAG risk. Stratification analyses indicated that the rs1143634 has a suggestive associated with high tension glaucoma (HTG) under dominant (P = 0.03), heterozygote (P = 0.04) and allelic models (P = 0.02), however, the weak association was nullified after Bonferroni adjustments for multiple tests.ConclusionsBased on current meta-analysis, we indicated that there is lack of association between the three SNPs of IL-1 and POAG. However, this conclusion should be interpreted with caution and further well designed studies with large sample-size are required to validate the conclusion as low statistical powers.

Expression QTL analysis of glaucoma endophenotypes in the Norfolk Island isolate provides evidence that immune-related genes are associated with optic disc size.

Primary open-angle glaucoma (POAG) is influenced by both genetic and environmental factors. Despite significant progress in identifying genetic variants associated with POAG, there remains a substantial amount of unexplained heritability. Study design features that may enhance knowledge of the genetic architecture include focusing on multiple quantitative traits related to ocular disorders (i.e. endophenotypes), targeting genetic variants that directly influence gene expression (i.e. cis-eQTLs) and utilising genetically isolated populations to reduce genetic and environmental noise and thus enhance association signals. In this study we performed heritability and blood-based eQTL association analysis of five key POAG endophenotypes in 330 individuals from the Norfolk Island (NI) isolate. Results showed evidence of heritability for all five traits, with H2 estimates ranging from 0.35 for intraocular pressure (IOP) to 0.82 for central corneal thickness (CCT) (P < 0.05). The primary finding was for BTN3A2, whereby both cis-SNP and transcript were significantly associated with disc size within a conditional regression model. Specifically, this model included rs853676 (β = 0.23,P = 0.008) and transcript (β = 0.23, P = 0.03). We also observed a cis-SNP association between optic disc size and LPCAT2 independent of transcript (P = 0.0004). These genes have specific functions in immune system pathways and suggest a role for an inherited immune component of POAG risk. This study also demonstrates an alternate approach to understanding the functional genetic basis of POAG and ocular health more generally.

A Multi-Locus Genetic Risk Score for Primary Open-Angle Glaucoma (POAG) Variants Is Associated with POAG Risk in a Mediterranean Population: Inverse Correlations with Plasma Vitamin C and E Concentrations.

Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. The genetics of POAG are complex, and population-specific effects have been reported. Although many polymorphisms associated with POAG risk have been reported, few studies have analyzed their additive effects. We investigated, in a southern European Mediterranean population, the association between relevant POAG polymorphisms, identified by initial genome-wide association studies (GWASs) and POAG risk, both separately and as an aggregated multi-locus genetic risk score (GRS). Also, bearing in mind that oxidative stress is a factor increasingly recognized in the pathogenesis of POAG, we analyzed the potential association of the GRS with plasma concentrations of antioxidant vitamins (C and E). We carried out a case–control study including 391 POAG cases and 383 healthy controls, and analyzed four genetic polymorphisms (rs4656461-TMCO1, rs4236601-CAV1/CAV2, rs2157719-CDKN2B-AS1 and rs3088440-CDKN2A). An unweighted GRS including the four non-linked polymorphisms was constructed. A strong association between the GRS and POAG risk was found. When three categories of the GRS were considered, subjects in the top category of the GRS were 2.92 (95% confidence interval (CI): 1.79–4.77) times more likely to have POAG compared with participants in the bottom category (p < 0.001). Moreover, the GRS was inversely correlated with plasma vitamin C (p = 0.002) and vitamin E (p = 0.001) concentrations, even after additional adjustment for POAG status. In conclusion, we have found a strong association between the GRS and POAG risk in this Mediterranean population. While the additional correlation found between GRS and low levels of vitamins C and E does not indicated a causal relationship, it does suggest the need for new and deeper research into the effects of oxidative stress as a potential mechanism for those associations.

Genetic Variant Near PLXDC2 Influences the Risk of Primary Open-angle Glaucoma by Increasing Intraocular Pressure in the Japanese Population.

The purpose of this study is to assess the association between the genetic variants that were previously reported to be associated with primary open-angle glaucoma (POAG) in the Japanese population and the phenotypic features. A total of 661 Japanese patients including 417 patients with POAG [normal tension glaucoma (NTG), n=210; high tension glaucoma (HTG), n=207] and 244 control subjects without glaucoma were analyzed for 3 genetic variants: rs547984 (near gene: ZP4), rs7081455 (PLXDC2), and rs7961953 (TMTC2). The allele frequency differences between POAG (NTG or HTG) patients and control subjects were estimated. The association between these genetic variants and the phenotypic features, including the maximum intraocular pressure (IOP) and the vertical cup-to-disc ratio, was evaluated. There was a significant difference in the rs7081455 (PLXDC2) allele frequencies between the POAG (P=0.0050) patients and the control subjects. An almost 1.5 increase in the risk of POAG (P=0.0042, odds ratio 1.52) was found with a G allele of rs7081455 (PLXDC2). The maximum IOP [23.5±10.3 mm Hg (mean±SD)] in patients with the GG genotype of rs7081455 (PLXDC2) was significantly higher (P=0.0037) than that (19.9±7.4 mm Hg) in patients with the TT genotype. The genetic variant near the PLXDC2 gene was found to influence the risk of POAG by increasing IOP in the Japanese population.

Type 2 diabetes mellitus and risk of open-angle glaucoma development in Koreans: An 11-year nationwide propensity-score-matched study

PurposeTo evaluate the risk of primary open-angle glaucoma (POAG) development in type 2 diabetes mellitus (T2DM) patients. MethodsIn this 11-year longitudinal study based on the Korean National Health Insurance research database, the data collected comprised 1,025,340 (2.2%) participants who were randomly selected from 46,605,433 Korean residents in 2002. The database was analyzed to identify participants with an initial diagnosis of T2DM in 2003–2004. The control group was composed of participants without T2DM who were propensity-score-matched, five controls per T2DM patient, according to age, gender, household income, residential area and underlying diseases, including hypertension, dyslipidaemia, coronary heart disease, cerebrovascular disease and thyroid disease. Cox proportional-hazards regression was used to calculate the overall hazard ratios (HRs) in participants with and without T2DM for development of POAG before and after adjusting for confounding factors. ResultsThere were 12,657 participants with T2DM and 63,285 propensity-score-matched controls without T2DM. POAG developed in 413 (3.3%) and 1188 (1.9%) participants in the T2DM and control groups, respectively. T2DM was associated with an increased risk of POAG development [HR: 1.80; 95% confidence interval (CI): 1.58–2.04] after adjusting for age, gender, household income and other potential confounders. ConclusionT2DM was significantly associated with the development of POAG after adjusting for potential confounders in the Korean population.

Genes of tumor necrosis factors and their receptors and the primary open angle glaucoma in the population of Central Russia

To examine the association of genetic polymorphisms (-308)G/A TNFα, (+250)A/G Ltα, (+36)A/G TNFR1, (+1663)A/G TNFR2 with the development of primary open angle glaucoma (POAG) among people in Central Russia. The study sample included 443 individuals, of which 252 patients with POAG and 191 individuals in the control group. Genotyping of (-308)G/A TNFα, (+250)A/G Ltα, (+36)A/G TNFR1, (+1663)A/G TNFR2 was performed using polymerase chain reaction. The distribution of alleles and genotypes of the studied DNA markers in the groups was examined by 2×2 contingency tables and χ2 with the Yates's correction for continuity and odds ratios (OR) with 95% confidence intervals (CI). Allele (-308)G TNFα (Р=0.01, OR=1.78, 95%CI 1.12-2.85) was identified as a risk factor for POAG. Homozygotes (-308) AA TNFα are at a lowest risk for development of the disease (Р=0.01, OR=0.0005). The following combination of genetic variants of cytokines were associated with a reduced risk of POAG: (+1663)A TNFR2 and (+250)G Ltα (OR=0.34). Genetic polymorphisms (-308)G/A TNFα, (+250)A/G Ltα, (+1663)A/G TNFR2 associated with the development of POAG in the population of Central Russia.

Primary Open-Angle Glaucoma Genetics in African Americans.

Individuals of African descent are at highest risk for developing primary open-angle glaucoma (POAG), a devastating disease and major contributor of blindness worldwide. Currently, there is a large dearth of knowledge in this area despite a critical need for better understanding the underlying genetic and environmental factors afflicting this population. Here we highlight the current literature exploring the genetics of POAG in African Americans. Current studies have yet to replicate European POAG index variants (i.e. CDKN2B-AS1 and SIX1/SIX6) in African Americans or to definitely exclude that these loci contribute to risk in African descent populations. Recent studies have evaluated clinical features that may account for some differences in POAG risk between African Americans and European Americans. In summary, little headway has been made in elucidating the genetics of primary open-angle glaucoma in African Americans and other individuals of African descent.

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OBJECTIVES/SPECIFIC AIMS: The overall goal of this project is to understand the genetic and clinical differences in POAG that specifically increase risk in individuals of African genetic ancestry. We will approach this goal by completing the following objectives: (i) localize a genetic signal that accounts for the significantly increased risk for primary open-angle glaucoma in African Americans and (ii) utilize electronic health records (EHR) data to expand our understanding of risk to incorporate endophenotypes of glaucoma and other clinically recorded variables that may influence disease risk. METHODS/STUDY POPULATION: We will genotype at least 200 available African American samples with glaucoma on the Illumina Infinium® Expanded Multi-Ethnic Genotyping Array (MEGAEX) and perform admixture mapping. We will then access EHR data to expand our analysis beyond glaucoma to encompass other relevant risk modifiers captured in the clinical record. RESULTS/ANTICIPATED RESULTS: We anticipate localizing a genetic signal or signals that may account for the increased POAG risk in African Americans. Our calculations indicate that we have ~81% power to detect association at a LOD score of 2 and a risk ratio of 2. Thus, we are well-powered to detect a true signal at this modest level of association DISCUSSION/SIGNIFICANCE OF IMPACT: This project will not only help to achieve precision medicine by filling in the gaps in knowledge regarding glaucoma in African Americans, but it will also address health disparities and aid in the realization of the full potential of “big data” so that all of these elements can be incorporated into a better understanding of health disparities.

Association of Toll-like receptor 4 single-nucleotide polymorphisms Asp299Gly and Thr399Ile with the risk of primary open angle glaucoma

Toll-like receptor 4 (TLR4) is a transmembrane receptor that mediates immune responses to exogenous and endogenous ligands. Previously, non-coding single nucleotide polymorphisms (SNPs) in the TLR4 gene were related to primary open angle glaucoma (POAG). This study was undertaken to investigate whether coding TLR4 Asp299Gly (rs4986790 A/G) and Thr399Ile (rs4986791 C/T) are associated with POAG in a Mexican population. One hundred and eighty-seven unrelated Mexican patients with POAG (94 men and 95 women; mean age 66.49 ± 14.3years) and 109 control subjects (40 men and 69 women; age, 63.28 ± 7.93years) were included. SNPs Asp299Gly (rs4986790 A/G) and Thr399Ile (rs4986791 C/T) were genotyped by a Taqman® Allelic Discrimination Assayand. Allelic, genotypic, haplotypic, and model-based (dominant, recessive, and codominant) associations of the SNPs with POAG were analyzed using Chi-squared tests or Fisher exact tests and logistic regression. Strong linkage disequilibrium was observed among the SNPs (D' = 0.8692), which were located in one haplotype block. With respect to allelic diversity, the minor allele of both SNPs generates a significantly increased risk of POAG. The minor allele of Asp299Gly conferred the highest increased risk of POAG (P = 0.0054, OR = 4.47, 95% CI = 1.46-13.70). With regard to genotypic diversity, individuals carrying the minor allele of Asp299Gly and Thr399Ile had a significant increased risk for POAG with OR of 4.47 (P = 0.054, 95% CI = 1.30-15.35) and 3.5, respectively (P = 0.012, 95% CI = 1.17-10.44). Haplotype analysis was non-significant. TLR4 coding SNPs Asp299Gly and Thr399Ile might be used as genetic susceptibility alleles for POAG in Mexican population. Our findings support the role of TLR4 in the pathophysiology of glaucoma.

New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics.

Primary open-angle glaucoma (POAG), the most common optic neuropathy, is a heritable disease. Siblings of POAG cases have a ten-fold increased risk of developing the disease. Intraocular pressure (IOP) and optic nerve head characteristics are used clinically to predict POAG risk. We conducted a genome-wide association meta-analysis of IOP and optic disc parameters and validated our findings in multiple sets of POAG cases and controls. Using imputation to the 1000 genomes (1000G) reference set, we identified 9 new genomic regions associated with vertical cup-disc ratio (VCDR) and 1 new region associated with IOP. Additionally, we found 5 novel loci for optic nerve cup area and 6 for disc area. Previously it was assumed that genetic variation influenced POAG either through IOP or via changes to the optic nerve head; here we present evidence that some genomic regions affect both IOP and the disc parameters. We characterized the effect of the novel loci through pathway analysis and found that pathways involved are not entirely distinct as assumed so far. Further, we identified a novel association between CDKN1A and POAG. Using a zebrafish model we show that six6b (associated with POAG and optic nerve head variation) alters the expression of cdkn1a. In summary, we have identified several novel genes influencing the major clinical risk predictors of POAG and showed that genetic variation in CDKN1A is important in POAG risk.

Glaucoma Risk Alleles in the Ocular Hypertension Treatment Study

Primary open-angle glaucoma (POAG) is a major cause of blindness and visual disability. Several genetic risk factors for POAG and optic nerve features have been identified. We measured the relative risk for glaucoma that these factors contribute to participants in the Ocular Hypertension Treatment Study (OHTS). Comparative series. One thousand fifty-seven of 1636 participants (65%) of the OHTS were enrolled in this genetics ancillary study. Samples of DNA were available from 1057 OHTS participants. Of these, 209 developed POAG (cases) and 848 did not develop glaucoma (controls) between 1994 and 2009. The frequencies of 13 risk alleles previously associated with POAG or with optic disc features in other cohorts were compared between POAG cases and controls in the OHTS cohort using analyses of variance. The 2 largest subgroups, non-Hispanic whites (n= 752; 70.7%) and blacks (n= 249, 23.7%), also were analyzed separately. The probability of glaucoma developing over the course of the OHTS was compared between participants stratified for transmembrane and coiled-coil domains 1 (TMCO1) risk alleles using Kaplan-Meier and Cox proportional hazards analyses. Association of POAG with known genetic factors. No association was detected between the known POAG risk alleles when the OHTS cohort was examined as a whole. However, in the subgroup of non-Hispanic whites, allele frequencies at the TMCO1 locus were statistically different between cases and controls (P= 0.00028). By 13 years, non-Hispanic white participants with TMCO1 risk alleles had a 12% higher cumulative frequency of glaucoma developing than participants with no TMCO1 risk alleles. Moreover, the Cox proportional hazard analysis demonstrated that TMCO1 alleles increased relative risk comparable with that of some previously analyzed clinical measures (i.e., intraocular pressure). The size of the OHTS cohort and its composition of 2 large racial subgroups may limit its power to detect some glaucoma risk factors. However, TMCO1 genotype was found to increase the risk of glaucoma developing among non-Hispanic whites, the largest racial subgroup in the OHTS cohort, at a magnitude similar to clinical predictors of disease that long have been associated with glaucoma.

Association of polymorphic variants of miRNA processing genes DGCR8 and XPO5 with primary open‐angle glaucoma risk in a Polish population

PurposeMany reports suggest the association between altered miRNA level and the pathogenesis of glaucoma. The single nucleotide polymorphisms in genes DGCR8 and XPO5, which are involved in microRNA biogenesis, may be the key factor in this process. The aim of this study was the analysis of the single nucleotide polymorphisms of DGCR8 and XPO5 genes, which are involved in miRNA processing pathway, in relations with primary open‐angle glaucoma (POAG).MethodsThe material used in the experiment was blood obtained from patients affected by primary open‐angle glaucoma and age matched controls. The control groups rs3757 DGCR8 and rs11077 XPO5 consisted of 135 and 140 subjects respectively. The rs3757 DGCR8 study group consisted of 137 patients, while rs11077 XPO5 number of patients was 138.The polymorphic variant frequencies of rs3757 and rs1107 were determined using DNA isolated from the peripheral blood lymphocytes in TaqMan® SNP Genotyping Assays.ResultsThe statistical analysis revealed that the genotype AG of DGCR8 rs3757 occurred more frequently in healthy individuals (p = 0.001), while homozygote GG was present mostly in people affected by primary open‐angle glaucoma (p = 0.003). No association between the risk of POAG and AC/CC genotypes of XPO5 was found.ConclusionsDuring the experiment it was evaluated that genotype AG in rs3757 DGCR8 exhibits protective effect, decreasing the risk of primary open angle glaucoma, while the homozygote GG probably is associated with increased risk of glaucoma. The analysis of polymorphic variants of the genes involved in miRNA biogenesis could enable people classification to high‐risk group. This work was supported by grant NCN no. 2012/05/B/NZ7/02502.

Prospective Study of Oral Health and Risk of Primary Open-Angle Glaucoma in Men: Data from the Health Professionals Follow-up Study

Tooth loss or periodontal disease is associated with systemic endothelial dysfunction, which has been implicated in primary open-angle glaucoma (POAG). The relationship between oral health and POAG has received limited attention. Thus, we evaluated the association between oral health history and risk of POAG and POAG subtypes. Prospective cohort study. Health Professionals Follow-up Study participants (40 536 men) followed biennially from 1986 to 2012. At each 2-year risk period, eligible participants were aged 40+ years, were free of POAG, and reported eye examinations. By using validated questions, we updated participants' status on number of natural teeth, teeth lost, periodontal disease with bone loss, and root canal treatments. During follow-up, 485 incident cases of POAG were confirmed with medical records and classified into subtypes defined by intraocular pressure (IOP; ≥ or <22 mmHg) or visual field (VF) loss pattern at diagnosis (peripheral loss only or early paracentral loss). Multivariable relative risks (MVRRs) and 95% confidence intervals (CIs) were estimated. Number of natural teeth, periodontal disease, and root canal treatment were not associated with POAG. However, compared with no report of tooth loss, a report of losing teeth within the past 2 years was associated with a 1.45-fold increased risk of POAG (95% CI, 1.06-1.97); in particular, a report within the past 2years of both losing teeth and having a prevalent diagnosis of periodontal disease was associated with a 1.85-fold increased risk of POAG (95% CI, 1.07-3.18). The associations with recent tooth loss were not significantly different for the POAG subtypes (P for heterogeneity ≥0.36), although associations were strongest in relation to the POAG subtypes with IOP <22 mmHg (MVRR, 1.93; 95% CI, 1.09-3.43) and early paracentral VF loss (MVRR, 2.27; 95% CI, 1.32-3.88). Although the number of natural teeth was not associated with risk of POAG, recent tooth loss was associated with an increased risk of POAG. Because these findings may be due to chance, they need confirmation in larger studies.

Associations of vitamin D deficiency and vitamin D receptor (Cdx-2, Fok I, Bsm I and Taq I) polymorphisms with the risk of primary open-angle glaucoma

BackgroundVitamin D deficiency and vitamin D receptor gene polymorphisms are known to be significantly associated with high myopia. Whether this genetic variant may impact primary open-angle glaucoma is largely unknown. This study investigated whether vitamin D receptor gene polymorphisms are altered in primary open-angle glaucoma subjects carrying the risk allele, and whether vitamin D deficiency is an important factor in the development of glaucoma.MethodsSeventy-three POAG patients and 71 age-matched controls from the Han population were enrolled. Serum levels of 1a, 25-Dihydroxyvitamin D3 were measured by enzyme-linked immunoabsorbent assay. Vitamin D receptor polymorphisms (Cdx-2, Fok I, Bsm I and Taq I) were analyzed using real-time polymerase-chain reaction high resolution melting analysis.ResultsSerum levels of 1a, 25-Dihydroxyvitamin in primary open-angle glaucoma patients were lower than in age-matched controls. Statistical analysis revealed a significant difference in the allelic frequencies of the BsmI and TaqI genotypes between primary open-angle glaucoma patients and age-matched controls, while other polymorphisms did not show any significant differences.ConclusionsVitamin D deficiency and the presence of the BsmI ‘B’ allele and the TaqI ‘t’ allele are relevant risk factors in the development of glaucoma.Trial registrationClinical Trials.gov: NCT02539745.The study was registered retrospectively on August 3rd, 2015. The first participant was enrolled on July 4th, 2013.

Venous thromboembolism does not share familial susceptibility with retinal vascular occlusion or glaucoma: a nationwide family study.

Inherited hypercoagulable states (i.e. thrombophilia) have been suggested to be involved in retinal vascular occlusion but results are divergent. Vascular micronutrition and ischemia have been hypothesised to be involved in the pathogenesis of glaucoma. This nationwide study determines the importance of family history of venous thromboembolism (VTE) as a risk factor for retinal vein occlusion (RVO), retinal artery occlusion (RAO), primary open angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). A total of 6,007,042 Swedish individuals were studied. Data from the Swedish Multigeneration Register for subjects aged 0-78years old for the period 1997-2010 were linked to the Swedish Hospital Discharge Register and the Hospital Outpatient Register. Main exposure measure was family history of VTE in first-degree relatives (parents and/or siblings). Main outcomes were hazard ratios (HRs) for RVO, RAO, POAG, and PACG. During follow-up 9036 individuals developed RVO, 2137 individuals developed RAO, 29,176 individuals developed POAG and 1498 individuals developed PACG. There was no association between family history of VTE and risk of RVO (HR=1.04, 95% CI 0.98-1.10), RAO (HR=1.00, 95% CI 0.89-1.13), POAG (HR=0.96, 95% CI 0.93-0.99), and PACG (HR=0.92, 95% CI 0.80-1.06) in the crude age and sex adjusted model. The results were similar in the fully adjusted model: RVO (HR=1.04, 95% CI 0.99-1.11), RAO (HR=1.01, 95% CI 0.89-1.13), POAG (HR=0.97, 95% CI 0.94-1.00), and PACG (HR=0.91, 95% CI 0.79-1.05). Family history of VTE is not a risk factor for RVO, RAO, POAG and PACG. Thus, it is unlikely that strong and common genetic variants associated with VTE are of importance for these disorders.

The association between cigarette smoking and primary open-angle glaucoma: a systematic review.

Glaucoma is one of the most common causes of irreversible blindness, globally. Findings from the Blue Mountain Eye Study suggest a moderate positive association between smoking and increased IOP (a significant risk factor for glaucoma). The previous two reviews investigating the association between smoking and primary open-angle glaucoma (POAG) show inconsistent findings and do not include recent studies investigating the dose-response effect of smoking. The current study aims to conduct an up-to-date, comprehensive evaluation of the existing literature. Identification of relevant existing literature was performed by an online search in MEDLINE for studies published from 1st January 1946 to 5th February 2015. The MESH headings (keywords) included "open-angle glaucoma" and "cigarette" or "smoking" or "tobacco". Two independent reviewers assessed the eligibility of each report based on predefined inclusion criteria. Odds ratios and 95% confidence intervals (95% CIs) were obtained from studies, for the change in risk of glaucoma due to both past and current smoking. Of the 26 abstracts reviewed, 17 papers were included in the final analysis. Nine of these were case-control studies, five cohort studies and three cross-sectional in design. Six of the case-control studies found a positive association between smoking and POAG, unlike the remaining studies. However, two relatively recent, large studies (including one prospective cohort study) investigating the effect of smoking dose have found a significant increase in risk of POAG in very heavy smokers. There is limited evidence for a causal association between tobacco smoking and POAG. The evidence for a link between current smoking and POAG appears stronger than that of past smoking, but recent studies suggest that heavy smoking may increase the risk of POAG. Future studies must further investigate the possible positive association between heavy smoking and POAG by stratifying participants by pack years and age.

Does Migraine Increase the Risk of Glaucoma?: A Population-Based Cohort Study.

This study investigated whether migraine influences the risk of primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG) in Taiwan.We retrieved the data analyzed in this study from the National Health Insurance Research Database in Taiwan. We included 17,606 newly diagnosed migraine patients without preexisting glaucoma and randomly selected and matched 70,423 subjects without migraine as the comparison cohort. The same exclusion criteria were also applied to comparison subjects. Multivariate Cox proportion-hazards regression model was used to assess the effects of migraines on the risk of glaucoma after adjusting for demographic characteristics and comorbidities.The cumulative incidence of POAG was higher in the migraine cohort than that in the comparison cohort (log-rank P = 0.04). The overall incidence of POAG (per 10,000 person-years) was 9.62 and 7.69, respectively, for migraine cohort and nonmigraine cohort (crude hazard ratio [HR] = 1.24, 95% confidence interval [CI] = 1.01–1.54). After adjusting the covariates, the risk of POAG was not significantly higher in the migraine cohort than in the comparison cohort (adjusted HR [aHR] = 1.15, 95% CI = 0.93–1.42). The cumulative incidence of PACG did not differ between the migraine cohort and the comparison cohort (log-rank test P = 0.53). The overall incidence of PACG was not significantly higher in the migraine cohort than that in the comparison cohort (7.42 vs 6.84 per 10,000 person-years), with an aHR of 1.04 (95% CI = 0.82–1.32).This study shows that migraines are not associated with a higher risk either in POAG or in PACG.

No Evidence of Association of Heterozygous Galactosylceramidase Deletion With Normal-Tension Glaucoma in a Korean Population.

A significant association between primary open-angle glaucoma risk and copy-number variation in the galactosylceramidase (GALC) gene was reported recently. This study investigated whether a heterozygous deletion of the GALC gene plays a significant role in normal-tension glaucoma (NTG) in Koreans. A 3-primer polymerase chain reaction assay was used to examine the heterozygous deletion of GALC in all Korean NTG cases (n=276) and controls (n=135). We did not identify any deletion variant of GALC gene in the NTG patients. This is the first copy-number variation study of the GALC gene in the Korean population with NTG. We demonstrated that a heterozygous GALC deletion does not play a significant role in the pathogenesis of NTG in a representative clinic-based population of South Koreans, unlike whites.

PPAR-γ and CYP46A1 genes polymorphism is associated with Primary Open Angle Glaucoma (POAG) in hypertensive North Indians

BackgroundInvolvement of genetic factors like gene polymorphisms was found to contribute significantly to development and progression of Primary Open Angle Glaucoma (POAG) in the last few decades. Aim of studyThe present study was carried out to investigate association of PPAR-γ (rs10865710) and CYP46A1 (rs754203) gene polymorphism with development of POAG in hypertensive North Indians. Patients and methodsStudy included 328 individuals, 226 as POAG cases and 102 controls. PPAR-γ and CYP46A1 gene polymorphism was evaluated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The genotypic and allelic frequency distribution in patients and controls was analyzed by SPSS (version 12.0). ResultsIn CYP46A1 gene polymorphism, TT genotype and T allele were found to be associated with a significantly decreased risk of POAG whereas the CT, CC genotypes and C allele were associated with an increased risk of POAG in both hypertensive and normotensive individuals. In PPAR-γ gene polymorphism, only GG genotype was nearly associated with POAG in only hypertensive cases. ConclusionsCYP46A1 (rs754203) gene polymorphism was associated with POAG in both hypertensive and normotensive patients whereas, only GG genotype of PPAR-γ (rs10865710) SNP shows significant association with POAG in hypertensive POAG patients.