Kunfang Wu

Association of genetic variation on chromosome 9p21 with polypoidal choroidal vasculopathy and neovascular age-related macular degeneration.

PURPOSE Polypoidal choroidal vasculopathy (PCV) contains aneurismal morphologic and histopathologic feature and it is considered to be a possible distinct entity from neovascular age-related macular degeneration (AMD). In this study, the association of identified risk variants for intracranial aneurysm on chromosome 9p21 with PCV and neovascular AMD in a Chinese Han population was investigated. METHODS The authors genotyped rs1333040 and rs10757278 on 9p21 in 177 PCV patients, 131 neovascular AMD patients, and 182 controls using a genotyping method and direct DNA sequencing. Allele and genotypes frequencies in the PCV and neovascular AMD groups were compared with controls using a free open-source software and binary logistic regression analysis. RESULTS Rs1333040 was not associated with PCV or neovascular AMD. Rs10757278 was significantly associated with PCV [risk allele: A, P (allelic) = 0.014; odds ratio = 1.44; 95% confidence interval, 1.08-1.94], but not associated with neovascular AMD. After adjusting for sex, age, smoking status, history of hypertension, type 2 diabetes, and coronary artery disease, the odds ratio for homozygous carriers of rs10757278-A was 2.10 (95% confidence interval, 1.14-3.85) for PCV. CONCLUSIONS The rs10757278 on chromosome 9p21 is significantly associated with the risk of PCV but not with neovascular AMD in the Chinese Han population.

Clinical Characteristics of Inflammatory Choroidal Neovascularization in a Chinese Population.

Abstract Purpose: To describe demographic features and clinical and imaging characteristics of inflammatory choroidal neovascularization (CNV) in a Chinese population. Methods: A retrospective case review of patients with CNV secondary to uveitis from 2002 to 2013. Results: A total of 125 patients (150 eyes, 166 CNVs; bifocal CNVs in 16 eyes), 64% of whom were women, were reviewed. The mean age was 35.86 years. The proportions of patients with punctate inner choroidopathy (PIC), multifocal choroiditis (MFC), and Vogt-Koyanagi-Harada (VKH) were 50.4, 22.4, and 8%. All of the cases were classic CNV in fluorocein angiography and type 2 CNV in OCT. The proportion of subfoveal lesions in active CNV (30.09%) was less than that in inactive CNV (60.38%). Conclusions: PIC, MFC, and VKH were the three primary specific types of uveitis with inflammatory CNV in this study. Inflammatory CNV tended to break though the retinal pigment epithelium and beneath the neurosensory retina. Moreover, inflammatory CNV was usually nonsubfoveal when it occurred.

Lack of Association with PEDF Met72Thr Variant in Neovascular Age-related Macular Degeneration and Polypoidal Choroidal Vasculopathy in a Han Chinese Population

Purpose: To investigate whether Met72Thr (rs1136287), a common single nucleotide polymorphism (SNP) variant of the pigment epithelium-derived factor (PEDF) gene, is associated with neovascular age-related macular degeneration (nAMD) or polypoidal choroidal vasculopathy (PCV) in a Han Chinese cohort. Methods: We genotyped Met72Thr (rs1136287) in persons of Han Chinese descent: 177 PCV patients, 131 nAMD patients, and 182 control persons. Genotyping was accomplished using the Multiplex SNaPshot system and by direct DNA sequencing. Genotypes and allele frequencies of patients and controls were evaluated for the SNP using PLINK software. Results: The minor allele frequency of the PEDF Met72Thr variant did not differ significantly between either PCV or nAMD and the control group: p = 0.3822 and p = 0.9822, respectively. The p-values for the additive, dominant, and recessive models were not statistically significant for PCV or nAMD. Conclusions: No evidence was found to support a role for the Met72Thr variant in susceptibility to either PCV or nAMD in a Han Chinese cohort.

An rs9621532 Variant Near the TIMP3 Gene is not Associated with Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy in a Chinese Han Population

Background: Recently, two genome-wide association studies with large cohorts both identified rs9621532, a new single nucleotide polymorphism (SNP) that is associated with advanced age-related macular degeneration (AMD) and located near the TIMP3 gene. Previous studies have demonstrated that AMD and polypoidal choroidal vasculopathy (PCV) share some common genetic background and that the incidence of PCV is higher in Asian populations than Caucasian populations. In this study, we aimed to investigate whether the rs9621532 SNP is associated with neovascular AMD (nAMD) and PCV in a Chinese Han population. Methods: We performed a case-control study in a Chinese Han population. The rs9621532 SNP was genotyped in 136 patients with nAMD, 195 patients with PCV, and 181 control individuals using the Multiplex SNaPshot system and the direct DNA sequencing technique. Rs9621532 genotypes and allele frequencies in the nAMD, PCV and control groups were evaluated using PLINK software. Results: In the nAMD, PCV, and control groups, the minor allele frequencies of the rs9621532 variant were 0.05147, 0.02564, and 0.03039, respectively. The rs9621532 SNP was not significantly associated with susceptibility to nAMD (p = 0.1773) or PCV (p = 0.6933). None of the p-values for the additive or dominant models were found to be statistically significant in the nAMD or PCV groups. No recessive homozygotes were genotyped in any of the three groups. Conclusions: No evidence was found to support an association between the rs9621532 variant and susceptibility to either nAMD or PCV in a Chinese Han population.

Macular pigment optical density in a healthy Chinese population.

To measure the macular pigment optical density (MPOD) values in a healthy Chinese population using the one‐wavelength reflectometry method and to investigate the relationships of MPOD with age, sex, body mass index (BMI), smoking and lens opacities.

The noninvasive retro-mode imaging modality of confocal scanning laser ophthalmoscopy in polypoidal choroidal vasculopathy: a preliminary application.

Purpose To evaluate the validity of the novel and noninvasive retro-mode imaging modality of confocal scanning laser ophthalmoscopy (cSLO) for detecting the morphological features of polypoidal choroidal vasculopathy (PCV). Design Prospective, observational, consecutive case series. Methods Twenty-six patients (29 eyes) with PCV were enrolled in this study. All patients underwent comprehensive ophthalmologic examinations and imaging studies, including retro-mode imaging, fundus autofluorescence (FAF), fundus photography, fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA) and spectral-domain optical coherence tomography (SD-OCT). We investigated the retro-mode images and compared the results with those of SD-OCT, FFA and ICGA. Results In the 29 PCV eyes, the retro-mode images clearly revealed polypoidal lesions in 27 (93.1%) eyes as well as branching vascular networks in 16 (55.2%) eyes. Others findings, including pigment epithelial detachment (PED) in 20 (69.0%) eyes, neuroretinal detachment (NRD) in 3 (10.3%) eyes, cystoid macular edema (CME) in 3 (10.3%) eyes, drusen in 4 (13.8%) eyes and minute granular changes of the retinal pigment epithelium (RPE) in 12 (41.3%) eyes, were also clearly visualized. When we compared the results with those of SD-OCT, FFA and ICGA, there was no significant difference between ICGA and retro-mode imaging for finding polypoidal lesions and (or) branching choroidal vascular networks (P>0.05). However, the rate of PED detection was significantly better with retro-mode imaging than with the ICGA (P<0.05). The differences were not statistically significant between SD-OCT and retro-mode imaging for detecting PED, NRD, CME, drusen and minute granular RPE changes (P>0.05). The differences were not statistically significant between FFA and retro-mode imaging for detecting PED, NRD, CME (P>0.05). Conclusions The novel and noninvasive retro-mode imaging by cSLO is able to clearly visualize the morphological features of PCV.

Three Variants of or near VEGF-A Gene are Not Associated with Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy in a Han Chinese Population

Abstract Purpose: To investigate whether three previously identified variants for age-related macular degeneration (AMD), the single nucleotide polymorphism (SNP) variants of or near the vascular endothelial growth factor A gene (VEGFA), were associated with neovascular AMD or polypoidal choroidal vasculopathy (PCV) in a Han Chinese cohort. Methods: This was a case-control study comprising 251 PCV patients, 157 neovascular AMD patients, and 204 control participants in a Han Chinese population. The rs833069, rs943080 and rs4711751 SNP were genotyped using the Multiplex SNaPshot system. Genotypes and allele frequencies of patients and controls were evaluated for the SNPs using PLINK software. Results: None of the allelic or genotypic effects of these three variants was significantly associated with PCV, neovascular AMD or combined both patient categories. Conclusions: No association was found to support the role for the rs833069, rs943080 and rs4711751 variants of or near VEGFA gene in susceptibility to either PCV or neovascular AMD in Han Chinese population. Further replication is necessary to validate these results.

Association of rs6982567 near GDF6 with neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in a Han Chinese cohort

BackgroundGrowth differentiation factor 6 (GDF6) has been reported to be a novel disease gene for age-related macular degeneration (AMD) in Caucasians. This study aimed to investigate whether rs6982567 was associated with neovascular AMD (nAMD) or polypoidal choroidal vasculopathy (PCV) in a Han Chinese cohort.MethodsA total of 612 participants (251 PCV patients, 157 nAMD patients and 204 controls) were included in this study. The SNaPshot system was used to genotype the rs6982567. PLINK software was used to evaluate the genotypes and allele frequencies of patients and controls.ResultsThe allele frequencies of rs6982567 were not significantly associated with nAMD, PCV or PCV and nAMD combined. Subjects with the TT genotype had a 2.42-fold greater risk of PCV (95% confidence interval, 1.07-5.43, p = 0.0290) than subjects with CC genotype. A recessive model of rs6982567 was statistically significantly associated with PCV (odds ratio, 2.29; 95% confidence interval, 1.04-5.05; p = 0.0351). However, the association did not withstand stringent Bonferroni correction. There were no significant differences in genotype distributions or models in nAMD.ConclusionsThere was a possible weak association between the rs6982567 near GDF6 and PCV in this replication study with an independent Han Chinese cohort. A complete survey of the GDF6 locus with a larger sample size is needed in future studies.

MMP9 Gene Polymorphism is not Associated with Polypoidal Choroidal Vasculopathy and Neovascular Age-related Macular Degeneration in a Chinese Han Population.

Abstract Background: Recently, one of our studies has revealed that the serum matrix metalloproteinase 9 (MMP9) level is elevated in polypoidal choroidal vasculopathy (PCV) but not in age-related macular degeneration (AMD). Previous studies have demonstrated that abnormal extracellular matrix (ECM) metabolism plays an important role in the pathogenesis of AMD and PCV. MMP9 is an important regulating enzyme in ECM metabolism, and the MMP9 gene may be a candidate gene for the susceptibility of PCV and AMD. In this study, we aimed to investigate whether the MMP9 gene polymorphism is associated with PCV and neovascular AMD (nAMD) in a Chinese Han population. Methods: We performed a case-control study in a Chinese Han population. Three tag single nucleotide polymorphisms (SNPs) (rs17576, rs3787268 and rs2274755) of the MMP9 gene were genotyped in 251 patients with PCV, 157 patients with nAMD, and 204 control individuals using the Multiplex SNaPshot system and the direct DNA sequencing technique. The three SNPs genotypes and allele frequencies in the PCV, nAMD and control groups were evaluated using PLINK software and binary logistic regression analysis. Results: In the PCV, nAMD, and control groups, the minor allele frequencies were 0.2099, 0.2070 and 0.2108 for the rs17576 variant; 0.4442, 0.4522 and 0.4461 for the rs3787268 variant; and 0.1036, 0.1338 and 0.1225 for the rs2274755 variant, respectively. The three tag SNPs were not significantly associated with susceptibility to PCV (p = 0.9524, 0.9553, and 0.3672, respectively) or nAMD (p = 0.9015, 0.8692, and 0.6543, respectively). None of the p values for the additive, dominant, or recessive models were statistically significant in the PCV or nAMD group. Conclusions: No evidence was found to support an association between the MMP9 gene variants and susceptibility to either nAMD or PCV in a Chinese Han population.

ENOS polymorphisms in neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in a Chinese Han population.

ABSTRACT Purpose: To investigate whether common genetic variants in the endothelial nitric oxide synthase gene (eNOS) are associated with neovascular age-related macular degeneration (nAMD) and polypoidal choroidalvasculopathy (PCV) in a Chinese Han population. Methods: DNA samples were obtained from 157 nAMD patients, 250 PCV patients and 204 healthy control subjects. Tag single nucleotide polymorphisms (SNPs) across the extended eNOS region were selected using data derived from the HapMap project. Genotyping of each tag SNP was performed by Multiplex SNaPshot system and direct DNA sequencing techniques. Genotypes and allele frequencies were evaluated with PLINK software for each group. Results: Seven SNPs for eNOS, rs1799983, rs1800783, rs3918186, rs3800787, rs3918188, rs7830, and rs3918227, were chosen as tag SNPs. Among these tag SNPs, rs1800783, rs3918186, rs3918188, and rs3918227 were not associated with nAMD or PCV. Rs1799983, rs3800787, and rs7830 was significantly associated with nAMD (p = 0.0192, 0.0170, and 0.0164, respectively), but not associated with PCV (p = 0.4852, 0.4568, and 0.4014, respectively). The discovered associations were no longer significant after Bonferroni correction. Conclusions: We found no sufficient evidence to support the role of any common eNOS variants in the susceptibility to nAMD or PCV in a Chinese Han population.