Association between PEDF gene polymorphisms and the risk of age-related macular degeneration.
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ABSTRACT:
SUBMITTER: Li Y
PROVIDER: S-EPMC6966057 | biostudies-literature | 2017
REPOSITORIES: biostudies-literature
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Project description:The aim of the present study was to evaluate the association between statin use and the risk of age-related macular degeneration (AMD). A systematic search of the PubMed, EMBASE and ISI web of science databases was used to identify eligible published literatures without language restrictions up to April 2015. Summary relative ratios (RRs) and 95% CIs were estimated using a fixed-effect or random-effects model. A total of 14 studies met the inclusion criteria and were included in this meta-analysis. No significant association was observed between statin use and the risk of any AMD (RR, 0.95; 95% CI, 0.74-1.15); and stratified analysis showed that statins had a significantly different effects on early and late stages of AMD. For early AMD, statin use significantly reduced the risk approximately 17% (RR, 0.83; 95% CI, 0.66-0.99). At the late stage, we observed a significant protective association of statin use with exudative AMD (RR, 0.90; 95% CI, 0.80-0.99), in contrast with the absent association between statins and geographic atrophy (RR, 1.16; 95% CI, 0.77-1.56). These results demonstrated that statin use was protective for early and exudative AMD. Additional large prospective cohort studies and RCTs are required to determine the potential effect of statins on AMD prevention.
| S-EPMC4677306 | biostudies-other
Project description:This study assesses the association of the pigment epithelium-derived factor (PEDF) gene with age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). Publications in MEDLINE and EMBASE up to 21/08/2014 were searched for case-control association studies of PEDF with AMD and/or PCV. Reported studies giving adequate genotype and/or allele information were included. Pooled odds ratios (OR) and 95% confidence intervals (CI) of each polymorphism were estimated. Our literature search yielded 297 records. After excluding duplicates and reports with incomplete information, 8 studies were eligible for meta-analysis, involving 2284 AMD patients versus 3416 controls, and 317 PCV patients versus 371 controls. Four PEDF polymorphisms were meta-analyzed: rs1136287, rs12150053, rs12948385 and rs9913583, but none was significantly associated with AMD or PCV. The most-investigated polymorphism, rs1136287, had a pooled-OR of 1.02 (95% CI: 0.94-1.11, P = 0.64) for AMD. In subgroup analysis by ethnicity, no significant association was identified. Polymorphisms present in single report showed no association. Therefore, existing data in literature does not support the role of PEDF in the genetic susceptibility of AMD and PCV, although replication in specific populations is warranted. Since the pooled-sample size for PCV was small, there is a need of PEDF genotyping in larger samples of PCV.
| S-EPMC4377572 | biostudies-literature
Project description:AIM:To systematically review the association between complement factors I (CFI) polymorphisms and age-related macular degeneration (AMD) and to explore whether CFI polymorphisms are associated with AMD. METHODS:Meta-analysis of articles published from 1995 to January 2015 of articles involved with AMD and polymorphisms of the CFI gene. Eligible data were pooled in a Meta-analysis, analyzing using STATA software (version 12.0), Review Manager (version 5.2) and different models based on the heterogeneity of effect sizes. Egger's test, Begg's rank correlation methods were used to evaluate for publication bias. RESULTS:Thirteen articles were eligible, describing two loci polymorphisms of the CFI gene (of which 12 articles focus on rs10033900T>C and 3 articles focus on rs2285714C>T). For rs10033900T>C, the results of our study revealed that having a mutant allele C, TC, CC and TC+CC was associated with a decreased risk of AMD in all population groups studied (C versus T models, OR=0.84, 95%CI: 0.72-0.99, P=0.04; TC versus TT models OR=0.89, 95%CI: 0.88-0.99, P=0.04; CC versus TT models, OR=0.76, 95%CI: 0.60-0.98, P=0.03; TC+CC versus TT models, OR=0.81, 95%CI:0.65-0.99, P=0.04). We found that C allele were related to lower AMD risk in the Caucasian population by subgroup analysis, but there was no association with AMD under the allele and genotypes comparison in Asian studies. For rs2285714 C>T, the TC, TT genotypes contributed to a higher risk of AMD, compared with the CC carriers and TC+CC (OR=1.34, 95%CI: 1.09-1.63, P=0.004; OR=1.50, 95%CI: 1.25-1.80, P<0.0001). CONCLUSION:This Meta-analysis suggests that CFI rs10033900T>C and rs2285714C>T polymorphisms may contribute to AMD.
| S-EPMC4761747 | biostudies-literature
Project description:To study the relationship between pigment epithelium-derived factor (PEDF) rs1136287, rs1894286 polymorphisms and the risk of age-related macular degeneration (AMD) in northern Chinese populations.The study was carried out on case-control methods. Ninety-six patients with AMD and 98 health controls were recruited who were matched with the former by age and gender, rs1136287 and rs1894286 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Hardy-Weinberg equilibrium (HWE) was also checked by ? test. The distribution frequencies of genotype, allele, and haplotype were calculated by direct counting method. The genotype, allele, and haplotype distribution differences between the case and control groups were analyzed by chi-square test, and odds ratio (OR) and 95% confidence interval (CI) was used to express the relative risk of AMD in northern Chinese populations. The linkage disequilibrium (LD) and haplotype analyses were conducted with Haploview software.The genotype and allele distribution frequencies in rs1136287 were obviously between in cases and controls (P?<?.05). TT genotype might lead to 3.24 times risk of AMD occurrence compared with CC genotype (OR?=?3.24, 95% CI?=?1.26-8.32), and C allele also played an increased risk role in the attack of AMD (OR?=?1.58, 95% CI?=?1.06-2.38). The T-C haplotype frequency of rs1136287-rs1894286 in PEDF were significantly correlated to the increased susceptibility to AMD (OR?=?1.57, 95% CI?=?1.02-2.40).The rs1136287 polymorphism in PEDF may be related to the occurrence risk of AMD. Additionally, a haplotype is also a non-ignorable risk factor.
| S-EPMC6113020 | biostudies-literature
Project description:BACKGROUND:Age-related macular degeneration (AMD) is the most common cause of irreversible visual loss in industrialized countries. Early symptoms of AMD include drusen and changes in retinal pigment epithelium. However, the etiology of AMD and drusen formation is not fully understood. Recent studies suggest that CYP2C8-related metabolic processes might play an important role in the development of AMD. The aim of our study is to investigate CYP2C8 rs10509681 and CYP2C8 rs11572080 genotype frequencies in patients with early AMD and to compare them with healthy controls. MATERIALS AND METHODS:The study enrolled 305 patients with early AMD and 300 healthy controls. The genotyping of CYP2C8 rs10509681 and CYP2C8 rs11572080 was carried out using the real-time PCR method. RESULTS:The analysis of studied CYP2C8 polymorphisms did not reveal any statistically significant differences between the AMD and the control groups. For the CYP2C8 rs10509681 gene polymorphism the distribution of T/T, T/C, and C/C genotypes was 83.3%, 16.7%, and 0% vs. 83.7%, 15.7%, and 0.7%, p = 0.343. For the CYP2C8 rs11572080 gene polymorphism the distribution of C/C, T/C and T/T and genotypes was 84.9%, 15.1%, and 0% vs. 82.3%, 17.3%, and 0.3%, p = 0.447. CONCLUSION:The study revealed that there were no statistically significant differences in the distribution of CYP2C8 rs10509681 and CYP2C8 rs11572080 genotypes in patients with early AMD and in healthy controls.
| S-EPMC5566945 | biostudies-literature
Project description:Age-related macular degeneration (AMD), a most common eye disease, can lead to irreversible visual impairment. Age, genetic and environmental factors have been implicated in AMD. Chemokine (C-X3-C motif) receptor 1 (CX3CR1) gene polymorphisms could influence the susceptibility of AMD.We tested the association between AMD and single nocleotide polymorphisms (SNPs) of CX3CR1 gene (rs3732378 and rs3732379) in 102 cases and 115 controls from China. Genotypes were determined by MassArray genotyping assay method. Association between CX3CR1 gene polymorphisms and AMD were examined by ?(2) test and logistic regression.Genotype distribution of CX3CR1 gene polymorphisms were in accordance with HWE examination. No obvious differences were observed in the genotypes of rs3732378 polymorphism between case and control groups (P>0.05), but A allele of it could increase the risk of AMD (P=0.025, OR=2.391, 95% CI=1.092-5.237). Both TT genotype and T allele of rs3732379 were significantly associated with the susceptibility of AMD (P=8.663, OR=8.663, 95% CI=1.044-71.874; P=0.021, OR=2.076, 95% CI=1.104-3.903). Age, gender and smoking status were used as common confounders to adjust the association between CX3CR1 gene polymorphism and AMD risk. Then we found that rs3732378 had no obvious association with AMD susceptibility. TT genotype of rs3732379 related to the occurrence of AMD, but the association was not significant (P=0.050, OR=8.274, 95% CI=1.002-69.963). T allele of rs3732379 might increase the susceptibility of AMD (P=0.029, OR=2.033, 95% CI=1.077-3.838).T allele of rs3732379 might have a positive association with the susceptibility of AMD.
| S-EPMC4583956 | biostudies-literature
Project description:PURPOSE: Using a candidate-gene approach, a recent case-control study identified a previously unknown association between neovascular age-related macular degeneration (AMD) and the coding Met72Thr variant in the pigment epithelium-derived factor (PEDF) gene in a Taiwan Chinese population. However, a subsequent replication study failed to see this association in a white European population. We noted an important difference in the sample ascertainment scheme between these two studies. The original study did not consider findings of indocyanine green (ICG) angiography for disease classification, which is the only way to obtain a clear image of polypoidal choroidal vasculopathy (PCV) lesions. This suggests that their cohort might include a considerable amount of PCV, given its high prevalence in the Chinese population. In contrast, the replication study intentionally excluded PCV from the case cohort on the basis of ICG angiograms. Therefore, the inconsistent finding might be caused by potential sample heterogeneity between these two studies. In this respect, this association needed to be examined in a case series of clearly defined individuals with neovascular AMD and PCV. The aim of this study was to validate the previously reported association of the PEDF Met72Thr variant in a well characterized Japanese population with neovascular AMD and PCV. METHODS: We genotyped the Met72Thr variant (rs1136287) in 116 patients with neovascular AMD, 140 patients with PCV, and 189 control participants in a Japanese population. Genotyping was performed using TaqMan technology. We tested for an association of this variant with neovascular AMD and PCV separately. We also evaluated population stratification in our study cohort. RESULTS: We found no statistically significant evidence for association between rs1136287 and either neovascular AMD or PCV under any genetic models (trend, genotypic, dominant, and recessive genetic models; p>0.05). Population structure analyses excluded stratification artifact in our study population. CONCLUSIONS: We report a lack of association between the PEDF Met72Thr variant and either neovascular AMD or PCV in a Japanese population. We conclude that the Met72Thr variant does not play a significant role in the risk of developing neovascular AMD or PCV.
| S-EPMC2690961 | biostudies-literature
Project description:Deficient 25-hydroxyvitamin D (25[OH]D) concentrations have been associated with increased odds of age-related macular degeneration (AMD).To examine whether this association is modified by genetic risk for AMD and whether there is an association between AMD and single-nucleotide polymorphisms of genes involved in vitamin D transport, metabolism, and genomic function.Postmenopausal women (N?=?913) who were participants of the Carotenoids in Age-Related Eye Disease Study (CAREDS) (aged 54 to <75 years) with available serum 25(OH)D concentrations (assessed October 1, 1993, to December 31, 1998), genetic data, and measures of AMD (n?=?142) assessed at CAREDS baseline from May 14, 2001, through January 31, 2004, were studied.Prevalent early or late AMD was determined from graded, stereoscopic fundus photographs. Logistic regression was used to estimate odds ratios (ORs) and 95% CIs for AMD by the joint effects of 25(OH)D (<12, ?12 to <20, ?20 to <30, and ?30 ng/mL) and risk genotype (noncarrier, 1 risk allele, or 2 risk alleles). The referent group was noncarriers with adequate vitamin D status (?30 ng/mL). Joint effect ORs were adjusted for age, smoking, iris pigmentation, self-reported cardiovascular disease, self-reported diabetes status, and hormone use. Additive and multiplicative interactions were assessed using the synergy index (SI) and an interaction term, respectively. To examine the association between AMD and variants in vitamin D-related genes, age-adjusted ORs and 95% CIs were estimated using logistic regression.Among the 913 women, 550 had adequate levels of vitamin D (?20 ng/mL), 275 had inadequate levels (?12 to <20 mg/mL), and 88 had deficient levels (<12 ng/mL). A 6.7-fold increased odds of AMD (95% CI,?1.6-28.2) was observed among women with deficient vitamin D status (25[OH]D <12 ng/mL) and 2 risk alleles for CFH Y402H (SI for additive interaction,?1.4; 95% CI,?1.1-1.7; P for multiplicative interaction?=?.25). Significant additive (SI,?1.4; 95% CI,?1.1-1.7) and multiplicative interactions (P?=?.02) were observed for deficient women with 2 high-risk CFI (rs10033900) alleles (OR,?6.3; 95% CI,?1.6-24.2). The odds of AMD did not differ by genotype of candidate vitamin D genes.In this study, the odds of AMD were highest in those with deficient vitamin D status and 2 risk alleles for the CFH and CFI genotypes, suggesting a synergistic effect between vitamin D status and complement cascade protein function. Limited sample size led to wide CIs. Findings may be due to chance or explained by residual confounding.
| S-EPMC4841267 | biostudies-literature
Project description:AimTo study polymorphisms in promotor regions of tumor necrosis factor (TNF)-α TNF-863A/C (rs1800630), TNF-308A/G (rs1800629), and TNF-238A/G (rs361525) in patients with age-related macular degeneration (AMD) and associations of complex TNF-α genotypes with AMD.MethodsOne hundred and two patients (82 women, 20 men; mean age 64.2±1.2y) with AMD and 100 healthy age- and sex-matched controls (82 women, 18 men; 60±1.4y) were included in the study. All subjects were Caucasian, all subjects and their parents were inhabitants of Russia. Genomic DNA was obtained from EDTA-preserved blood using the standard phenol-chloroform method. Polymorphisms were detected by polymerase chain reaction followed by the restriction fragment length polymorphism method. The following TNF-α genotypes were studied: TNF-α-238 AA, GA, GG, TNF-α-308 AA, GA, GG, TNF-α-863 AA, CA, CC.ResultsDifferences in TNF-α-863 and TNF-α-238 genotypes frequencies in patients with AMD and healthy controls were not found. The distribution of TNF-α-308 AA and TNF-α-308 GA genotypes was significantly different between the studied group and the controls [odds ratios (OR) =0.22, P=0.0287 and OR=2.91, P=0.0063, respectively]. TNF-863CC/TNF-308GA and TNF-308GA/TNF-238GG genotypes were associated with the increased risk of AMD (OR=2.48, P=0.0332 and OR=2.51, P=0.0187, respectively). Five genotypes combinations appeared to be protective.ConclusionIn the present study, single nucleotide polymorphisms and complex polymorphisms of one of the key inflammatory cytokines TNF-α, and a number of significant associations of these polymorphisms with AMD in Russian population have been shown. Complex analysis of genotypes could be important in AMD risk factors detection and studying pathogenesis.
| S-EPMC6326924 | biostudies-literature
Project description:BACKGROUND Age-related macular degeneration (AMD) is the leading cause of blindness in people aged 65 years and older in developed countries. The pathogenesis of AMD has been linked to mechanisms involving inflammation, oxidative stress, and basal laminar deposit formation between retinal pigment epithelium (RPE) cells and the basal membrane, caused by advanced glycation end products (AGEs). AGEs are implicated in the pathogenesis of AMD through the AGE-and receptor for AGE (RAGE) interaction, which can be altered by polymorphisms of the RAGE gene. We examined RAGE rs1800624 and rs1800625 gene polymorphisms contributing to AMD development. MATERIAL AND METHODS The study enrolled 300 patients with early AMD, 300 patients with exudative AMD, and 800 healthy controls. The genotyping was carried out using the RT-PCR method. RESULTS The analysis of two single nucleotide polymorphisms (SNPs) in the RAGE gene showed that rs1800624 was associated with a 1.6-fold decreased risk for exudative AMD under the dominant model after adjustment for age (OR=0.616; 95% CI: 0.394-0.963; p=0.034) and each copy of allele T at rs1800624 was associated with a 1.4-fold decreased risk for exudative AMD development under the additive model after adjustment for age (OR=0.701; 95% CI: 0.510-0.962; p=0.028). Analysis revealed that the rs1800625 allele G at rs1800625 was associated with a 1.5-fold increased risk for exudative AMD after adjustment for age (OR=1.545; 95% CI: 1.003-2.379; p=0.048). These results suggested that the allele G at rs1800625 was a risk-allele for exudative AMD development. In haplotype analysis, A-G haplotype was significantly more frequently observed in exudative AMD patients compared to healthy controls (3.3% versus 1.4%, p=0.035). CONCLUSIONS We revealed a significant association between RAGE gene rs1800624 and rs1800625 polymorphisms and AMD risk. We considered T allele at rs1800624 to be protective against AMD development, while allele G at rs1800625 was considered to be a marker of poor prognosis in AMD development.
| S-EPMC5771184 | biostudies-literature