Association between Active Helicobacter pylori Infection and Glaucoma: A Systematic Review and Meta-Analysis.
ABSTRACT: Background: Glaucoma is the second most common cause of blindness worldwide affecting almost 70 million individuals. Helicobacter pylori (H. pylori) is a widespread pathogen with systematic pathogenicity. This meta-analysis aimed to estimate the contradictory data regarding a potential association between active H. pylori infection and glaucoma. Materials and Methods: A research in MEDLINE/PubMed and Google Scholar was conducted and original studies investigating the relationship between H. pylori infection and glaucoma were included. Analysis was performed with random effects model. The main outcome was the odds ratio (OR) with 95% confidence intervals (CI) of H. pylori infection as a risk factor for glaucoma. A parallel analysis studied the role of active infection as indicated by histology and the titer of anti-H. pylori antibodies. For the anti-H. pylori antibody titers, weighted mean differences (WMD) were estimated between patients and controls. Results: Fifteen studies were included, with 2664 participants (872 patients with glaucoma and 1792 controls), divided into primary open-angle glaucoma (POAG), normal tension glaucoma (NTG) and pseudo-exfoliation glaucoma (PEG). The association between H. pylori infection and overall glaucoma was significant (OR = 2.08, CI 95% 1.48-2.93) with moderate heterogeneity (I2 = 61.54%). After stratification by glaucoma subtype, heterogeneity was eliminated in the NTG subgroup. Studies with healthy controls, and controls with anemia yielded very low or no heterogeneity, respectively. Gastric biopsy to document active H. pylori infection yielded the highest OR (5.4, CI: 3.17-9.2, p < 0.001) and null heterogeneity. For anti-H. pylori antibody titers, there was a significant difference in WMD between patients and controls (WMD 15.98 IU/mL; 95% CI: 4.09-27.87; p = 0.008); values were greater in glaucoma patients, with high heterogeneity (I2: 93.8%). Meta-regression analysis showed that mean age had a significant impact on glaucoma (p = 0.037). Conclusions: Active H. pylori infection may be associated with glaucoma with null heterogeneity, as, beyond histology, quantified by anti-H. pylori titers and increases with age.
Project description:<h4>Background</h4>Genetic polymorphisms of the Optic atrophy 1 gene have been implicated in altering the risk of primary open angle glaucoma (POAG), especially the susceptibility to normal tension glaucoma (NTG), but the results remain controversial.<h4>Methods</h4>Multiple electronic databases (up to January 20, 2012) were searched independently by two investigators. A meta-analysis was performed on the association between Optic atrophy 1 polymorphisms (rs 166850 and rs 10451941) and normal tension glaucoma (NTG)/high tension glaucoma (HTG). Summary odds ratios (ORs) and 95% confidence intervals (CI) were estimated.<h4>Results</h4>Seven studies of 713 cases and 964 controls for NTG and five studies of 1200 cases and 971 controls for HTG on IVS8+4C>T (rs 166850) and IVS8+32T>C (rs10451941) were identified. There were significant associations between the OPA1 rs10451941polymorphism and NTG susceptibility for all genetic models(C vs. T OR = 1.26, 95% CI 1.09-1.47, p = 0.002; CC vs. TT: OR = 1.52, 95% CI 1.04-2.20, p = 0.029; CC vs. CT+TT: OR = 1.64, 95% CI 1.16-2.33, p = 0.005; CC+CT vs. TT: OR = 1.21, 95% CI 1.02-1.44, p = 0.032). However, no evidence of associations was detected between the OPA1 IVS8+32C>T polymorphism and POAG susceptibility to HTG. Similarly, clear associations between the rs 166850 variant and NTG were observed in allelic and dominant models (T vs. C OR = 1.52, 95% CI 1.16-1.99, p = 0.002; TT+TC vs. CC OR = 1.50, 95% CI 1.13-2.01, p = 0.006) but not to HTG. In subgroup analyses by ethnicity, we detected an association between both OPA1 polymorphisms and risk for NTG in Caucasians but not in Asians. By contrast, no significant findings were noted between OPA1 variants for HTG, either in Caucasians or in Asians.<h4>Conclusions</h4>Both the IVS8+4C>T and IVS8+32T>C variants may affect individual susceptibility to NTG. Moreover, stratified analyses for NTG detecting the effects of both OPA1 polymorphisms seemed to vary with ethnicity. Further investigations are needed to validate the association.
Project description:Although intraocular pressure (IOP) is the most definitive cause of glaucoma, a subtype of open angle glaucoma (OAG) termed normal tension glaucoma (NTG), which occurs in spite of normal IOP, accounts for a large part of glaucoma cases, especially in Japan. To find common genetic variants contributing to NTG in Japanese patients, we conducted a genome-wide association study (GWAS). We performed the first screening for 531,009 autosomal SNPs with a discovery cohort of 286 cases and 557 controls, and then a second screening for the top 30 suggestive loci in an independent cohort of 183 cases and 514 controls. Our findings identified a significantly associated SNP; rs523096 [combined p-value?=?7.40×?10(-8), odds ratio (OR)=?2.00 with 95% confidence interval (CI) 1.55-2.58] located 10 kbp upstream of CDKN2B on chromosome 9p21. Moreover, analysis of another independent case-control set successfully replicated the results of the screening studies (combined values of all 3 stages p?=?4.96?×?10(-11), OR=?2.13 with 95% CI 1.69-2.68). The SNPs near rs523096 were recently reported to be associated with OAG associated with elevated IOP in primary open-angle glaucoma (POAG), the predominant subtype of glaucoma in Caucasian populations. Our results revealed that the 9p21 locus is also associated with NTG in Japanese. In addition, we identified SNPs more strongly associated with NTG.
Project description:To evaluate the association between refractive error and the prevalence of glaucoma by race or ethnicity.Cross-sectional study.Kaiser Permanente Northern California Health Plan members with refractive error measured at 35 years of age or older between 2008 and 2014 and with no history of cataract surgery, refractive surgery, or a corneal disorder.We identified 34 040 members with glaucoma or ocular hypertension (OHTN; cases) and 403 398 members without glaucoma (controls). Glaucoma cases were classified as primary angle-closure glaucoma (PACG); 1 of the 4 forms of open-angle glaucoma: primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), pigmentary glaucoma (PIGM), and pseudoexfoliation glaucoma (PEX); or OHTN. Refractive error, expressed as spherical equivalent (SE), was coded as a continuous trait and also as categories. Logistic regression analyses were used to estimate the association between refractive error and the prevalence of glaucoma overall and in specific racial or ethnic groups.The association between refractive error and glaucoma subtypes evaluated as odds ratios (ORs) with 95% confidence intervals (CIs).In controls, the mean SE was -0.59 diopters (D) (standard deviation, 2.62 D). Each 1-D reduction in SE was associated with a 22% decrease in the odds of PACG (OR, 0.78; 95% CI, 0.77-0.80) and with increases in the odds of open-angle glaucoma ranging from 1.23 (95% CI, 1.20-1.26) for PIGM, to 1.07 (95% CI, 1.03-1.11) for PEX, and to 1.05 (95% CI, 1.04-1.06) for OHTN. In addition, we observed a stronger association between myopia and POAG among non-Hispanic whites (OR, 1.12; 95% CI, 1.11-1.13) and NTG among Asians (OR, 1.17; 95% CI, 1.15-1.20) and non-Hispanic whites (OR, 1.19; 95% CI, 1.15-1.22).Myopia was associated with an increased prevalence of all forms of open-angle glaucoma and OHTN, whereas hyperopia was associated with a substantially increased prevalence of PACG. Although high myopia is a strong risk factor for glaucoma subtypes, low and moderate myopia also have a significant effect on glaucoma risk. Additionally, there were moderate racial differences in the association of myopia with the risk of POAG and NTG.
Project description:Purpose. To investigate the potential relationship between open-angle glaucoma (OAG) and peripapillary choroidal thickness (PPCT). Materials and Methods. Relevant publications were searched systematically through various databases from inception to January 2016. Studies comparing PPCT in OAG patients and healthy controls were retrieved. All qualified articles were analyzed using Stata 14.0 and Revman 5.3 software. Results. A total of 13 studies were identified for inclusion. There was a significant reduction of average PPCT in OAG patients compared to control participants (WMD = -24.07, 95% CI: -34.29, -13.85). Reduction of PPCT was significant in the superior (WMD = -28.87, 95% CI: -44.96, -12.78) and nasal (WMD = -21.75, 95% CI: -41.52, -1.98) sectors, but there was no significant reduction of PPCT in the inferior (WMD = -9.57, 95% CI: -36.55, 17.40) and temporal (WMD = -13.85, 95% CI: -35.40, 7.70) sectors. No obvious publication bias was detected. Conclusions. This meta-analysis suggests that open-angle glaucoma patients have significantly decreased peripapillary choroidal thickness compared to healthy individuals. Peripapillary choroidal thickness measured by optical coherence tomography may be an important parameter to consider in open-angle glaucoma.
Project description:Importance:Mutations in the myocilin (MYOC) gene are the most common molecularly defined cause of primary open-angle glaucoma that typically occurs in patients with high intraocular pressures (IOP). One MYOC mutation, p.Gln368Ter, has been associated with as many as 1.6% of primary open-angle glaucoma cases that had a mean maximum recorded IOP of 30 mm Hg. However, to our knowledge, the role of the p.Gln368Ter mutation in patients with normal-tension glaucoma (NTG) with an IOP of 21 mm Hg or lower has not been investigated. Objective:To evaluate the role of the p.Gln368Ter MYOC mutation in patients with NTG. Design, Setting, and Participants:In this case-control study of the prevalence of the p.Gln368Ter mutation in patients with NTG, cohort 1 was composed of 772 patients with NTG and 2152 controls from the United States (Iowa, Minnesota, and New York) and England and cohort 2 was composed of 561 patients with NTG and 2606 controls from the Massachusetts Eye and Ear Infirmary and the NEIGHBORHOOD consortium. Genotyping was conducted using real-time polymerase chain reaction that was confirmed with Sanger sequencing, the imputation of genome-wide association study data, or an analysis of whole-exome sequence data. Data analysis occurred between April 2007 and April 2018. Main Outcomes and Measures:Comparison of the frequency of the p.Gln368Ter MYOC mutation between NTG cases and controls with the Fisher exact test. Results:Of 6091 total participants, 3346 (54.9%) were women and 5799 (95.2%) were white. We detected the p.Gln368Ter mutation in 7 of 772 patients with NTG (0.91%) and 7 of 2152 controls (0.33%) in cohort 1 (P?=?.03). In cohort 2, we detected the p.Gln368Ter mutation in 4 of 561 patients with NTG (0.71%) and 10 of 2606 controls (0.38%; P?=?.15). When the cohorts were analyzed as a group, the p.Gln368Ter mutation was associated with NTG (odds ratio, 2.3; 95% CI, 0.98-5.3; P?=?.04). Conclusions and Relevance:In cohorts 1 and 2, the p.Gln368Ter mutation in MYOC was found in patients with IOPs that were 21 mm Hg or lower (NTG), although at a frequency that is lower than previously detected in patients with higher IOP. These data suggest that the p.Gln368Ter mutation may be associated with glaucoma in patients with normal IOPs as well as in patients with IOPs that are greater than 21 mm Hg.
Project description:BACKGROUND:Primary open angle glaucoma is a progressive optic neuropathy characterised by the selective loss of retinal ganglion cells, pathological optic disc cupping and visual field defects. The OPA1 gene encodes an inner mitochondrial membrane protein crucial for normal mitochondrial function, and pathogenic mutations cause autosomal dominant optic atrophy by specifically targeting retinal ganglion cells. This raises the distinct possibility that more subtle genetic variations in OPA1 could alter the risk of developing glaucoma. METHODS:137 patients with primary open angle glaucoma (67 patients with high-tension glaucoma (HTG), 70 patients with normal-tension glaucoma (NTG)) and 75 controls from the North East of England were studied. Three single-nucleotide polymorphisms in intron 8 (IVS8+4c-->t and IVS8+32t-->c) and exon 4 (c.473A-->G) of the OPA1 gene were genotyped in the study group. In addition, the entire OPA1 coding region was sequenced in 24 individuals with the CT/TT compound genotype using standard BigDye chemistries. RESULTS:There was no difference in either allele or genotype frequency for the IVS8+32t-->c single-nucleotide polymorphisms between patients and controls, but there was a significant association between the T allele at IVS8+4c-->t and the risk of developing NTG (OR=2.04, 95% CI=1.10 to 3.81, p=0.004), but not HTG. Logistic regression analysis also confirmed a strong association between the CT/TT compound genotype at IVS8+4 and IVS8+32 with NTG (OR=29.75, 95% CI=3.83 to 231.21, p=0.001). CONCLUSIONS:The CT/TT compound genotype at IVS8+4 and IVS8+32 is a strong genetic risk determinant for NTG but not HTG.
Project description:The caveolin 1 to caveolin 2 (CAV1-CAV2) gene region on chromosome 7q31 has been reported to be associated with susceptibility to primary open angle glaucoma (POAG) and normal tension glaucoma (NTG) in previous studies. We investigated whether genetic variants in the CAV1-CAV2 region are associated with NTG in Japanese patients. Two hundred and ninety-two Japanese patients with NTG and 352 Japanese healthy controls were recruited. We genotyped three single-nucleotide polymorphisms; that is, rs1052990, rs4236601, and rs7795356, in the CAV1-CAV2 gene region and assessed the allelic diversity among cases and controls. The frequency of the minor allele (G) of rs1052990 was significantly decreased in NTG cases compared with controls (P=0.014, OR=0.71), whereas NTG or POAG cases had a significantly higher frequency of the allele than controls in previous studies. Conversely, rs7795356 did not show any significant association with NTG cases, and rs4236601 was monomorphic in the Japanese study population. Our findings did not correspond with previous positive results, suggesting that CAV1-CAV2 variants studied in the present study are not important risk factors for NTG susceptibility in all populations. Further studies are needed to elucidate the possible contribution of the CAV1-CAV2 region to the development of glaucoma.
Project description:BACKGROUND:It is reported that glaucoma may be associated with vascular dysregulation. Normal tension glaucoma (NTG) and primary open angle glaucoma (POAG), which feature different intraocular pressure levels, may manifest differential features of systemic autonomic dysregulation. METHODS AND RESULTS:We investigated autonomic regulation to carbohydrate ingestion and postural change in 37 glaucoma patients (19 NTG and 18 POAG) and 36 controls. Subjects were age and gender-matched, normotensive, and had normal comparable insulin sensitivity. Continuous finger arterial pressure and ECG was recorded in supine and standing positions before and after carbohydrate ingestion. Low frequency (LF, 0.04-0.15Hz) and high frequency (HF, 0.15-0.4Hz) spectral power of heart rate and systolic blood pressure variability (HRV and SBPV) were calculated to estimate sympathovagal function. Overall comparison glaucoma (N = 37) and controls (N = 36) showed an increased sympathetic excitation, vagal withdrawal and unstable mean arterial pressure after carbohydrate ingestion in glaucoma patients. Glaucoma severity by retinal nerve fibre layer (RNFL) thickness is positively correlated to autonomic responses (HRV LF power and HF power in normalised units (nu), and HRV LF/HF ratio) after carbohydrate ingestion. Early (30 minutes) following carbohydrate ingestion, SBP LF power and HRV parameters remained unchanged in controls; while POAG showed abnormal autonomic responses, with a paradoxical vagal enhancement (increased HRV HF power in nu) and sympathetic inhibition (decreased HRV LF power nu and HRV LF/HF ratio), and associated hypotension. Later (60-120 minutes) following carbohydrate ingestion, HRV parameters remained unaltered in controls; whereas NTG manifested vagal withdrawal (reduced HRV HF power nu) and sympathetic hyper-responsiveness (increased HRV LF power nu and HRV LF/HF ratio), despite increased SBP LF power in both controls and NTG. Both NTG and POAG exhibited attenuated autonomic responses to postural stress. CONCLUSIONS:NTG and POAG both manifest some systemic autonomic cardiovascular dysregulation. However, the two forms of glaucoma respond differentially to carbohydrate ingestion, irrespective of insulin resistance.
Project description:Glaucoma is the most common cause of irreversible blindness worldwide. One subset of glaucoma, normal tension glaucoma (NTG) occurs in the absence of high intraocular pressure. Mutations in two genes, optineurin (OPTN) and TANK binding kinase 1 (TBK1), cause familial NTG and have known roles in the catabolic cellular process autophagy. TKB1 encodes a kinase that phosphorylates OPTN, an autophagy receptor, which ultimately activates autophagy. The sequestosome (SQSTM1) gene also encodes an autophagy receptor and also is a target of TBK1 phosphorylation. Consequently, we hypothesized that mutations in SQSTM1 may also cause NTG. We tested this hypothesis by searching for glaucoma-causing mutations in a cohort of NTG patients (n = 308) and matched controls (n = 157) using Sanger sequencing. An additional 1098 population control samples were also analyzed using whole exome sequencing. A total of 17 non-synonymous mutations were detected which were not significantly skewed between cases and controls when analyzed separately, or as a group (p > 0.05). These data suggest that SQSTM1 mutations are not a common cause of NTG.
Project description:BACKGROUND:The association of the WDR36 gene with glaucoma has been controversial in the literature. We therefore conducted a systematic review and meta-analysis to assess the association of all reported common polymorphisms in WDR36 with primary open angle glaucoma (POAG) and its subtypes: high tension glaucoma (HTG) and normal tension glaucoma (NTG). METHODS:Publications in PUBMED and EMBASE databases up to March 9, 2016 were searched for case-control association studies of WDR36 with POAG, HTG, and/or NTG. Reported studies giving adequate genotype and/or allele information were included. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) of individual polymorphisms were estimated using the allelic model. RESULTS:Our literature search yielded 122 records, among which 5 studies were eligible for meta-analysis, involving a total of 1352 POAG patients and 894 controls. Five WDR36 polymorphisms were meta-analyzed, rs11241095, rs10038177, rs17553936, rs13186912, and rs13153937. However, none of them was significantly associated with POAG, HTG, or NTG. The most-investigated polymorphisms, rs11241095 and rs10038177, had a pooled-OR of 1.09 (95% CI: 0.94-1.28, P?=?.25, I?=?0) and 0.99 (95% CI: 0.71-1.39, P?=?.97, I?=?77%), respectively, for POAG. CONCLUSION:The existing data in the literature do not support a significant role of WDR36 in the genetic susceptibility of POAG or its subtypes. Further replication studies in specific populations are warranted.