Dataset Information

Association between PEDF gene polymorphisms and the risk of age-related macular degeneration.

ABSTRACT: OBJECTIVE:Pigment epithelium-derived factor (PEDF) strongly inhibits angiogenesis, and plays an important role in retinoblastoma cells. In this study we detect the association of PEDF gene polymorphisms (rs1136287 and rs12150053) and age-related macular degeneration (AMD) risk. METHODS:This is a case-control study including 118 AMD patients and 121 healthy controls. PEDF gene polymorphisms were genotyped by TaqMan method. Hardy-Weinberg equilibrium (HWE) was used to detect the representativeness of the cases and controls. Differences of genotype and allele distributions of PEDF polymorphisms were calculated by Chi-square test. Odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were used to present the relative risk of AMD. RESULTS:Genotype and allele distributions in controls were in accordance with HWE. Genotype and allele distributions of rs1136287 had no significant association with the susceptibility of AMD under five contrast models (P<0.05). CC genotype and C allele of rs12150053 were higher in cases than that in controls, and rs12150053 was obviously related to the risk of AMD under T vs. C model (P=0.044, OR=1.499, 95% CI=1.009-2.226). CONCLUSION:In this study, there was no obvious association between PEDF gene rs1136287 polymorphism and AMD susceptibility, and rs12150053T might act as a susceptible allele in the occurrence of AMD.

SUBMITTER: Li Y

PROVIDER: S-EPMC6966057 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association between <i>PEDF</i> gene polymorphisms and the risk of age-related macular degeneration.

Li Yuanyuan Y Wang Deliang D

International journal of clinical and experimental pathology 20171201 12

<h4>Objective</h4>Pigment epithelium-derived factor (PEDF) strongly inhibits angiogenesis, and plays an important role in retinoblastoma cells. In this study we detect the association of <i>PEDF</i> gene polymorphisms (rs1136287 and rs12150053) and age-related macular degeneration (AMD) risk.<h4>Methods</h4>This is a case-control study including 118 AMD patients and 121 healthy controls. <i>PEDF</i> gene polymorphisms were genotyped by TaqMan method. Hardy-Weinberg equilibrium (HWE) was used to ...[more]

PMID: 31966545

Similar Datasets

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.

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.

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.

Dataset Information

Association between PEDF gene polymorphisms and the risk of age-related macular degeneration.

Publications

Association between <i>PEDF</i> gene polymorphisms and the risk of age-related macular degeneration.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets