Dataset Information

No association of age-related maculopathy susceptibility protein 2/HtrA serine peptidase 1 or complement factor H polymorphisms with early age-related maculopathy in a Chinese cohort.

ABSTRACT: PURPOSE: Single nucleotide polymorphisms (SNPs) of age-related maculopathy susceptibility protein 2/HtrA serine peptidase 1 (ARMS2/HTRA1) and complement factor H (CFH) have been reported to be associated with age-related macular degeneration (AMD). The purpose of this study was to investigate the association of ARMS2/HTRA1 and CFH SNPs with early age-related maculopathy (ARM) in a Han Chinese cohort. METHODS: The cohort consisted of 315 unrelated subjects, including 158 patients with early ARM and 157 recruited controls. Early ARM was diagnosed and graded according to the Age-Related Eye Disease Study criteria. Four SNPs in ARMS2/HTRA1 and six SNPs in CFH previously reported to be associated with AMD were genotyped using TaqMan genotyping assays. Logistic regression implemented with the R statistical language was used for association analysis. RESULTS: None of the ARMS2/HTRA1 and CFH SNPs showed any significant association with early ARM (all p>0.453), with the odds ratios ranging from 0.88 to 1.17. None of the SNPs were associated with unilateral or bilateral early ARM or any grade of early ARM (all p>0.249). CONCLUSIONS: The association of ARMS2/HTRA1 and CFH SNPs in early ARM was not detected in our cohort. The findings in the current study indicated that the effects of ARMS2/HTRA1 and CFH in early ARM could be much lower compared to those in AMD.

SUBMITTER: Chen JH

PROVIDER: S-EPMC3654849 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

No association of age-related maculopathy susceptibility protein 2/HtrA serine peptidase 1 or complement factor H polymorphisms with early age-related maculopathy in a Chinese cohort.

Chen Jian-Huan JH Yang Yunli Y Zheng Yuqian Y Qiu Minghui M Xie Mingliang M Lin Wenjie W Zhang Mingzhi M Pang Chi Pui CP Chen Haoyu H

Molecular vision 20130501

<h4>Purpose</h4>Single nucleotide polymorphisms (SNPs) of age-related maculopathy susceptibility protein 2/HtrA serine peptidase 1 (ARMS2/HTRA1) and complement factor H (CFH) have been reported to be associated with age-related macular degeneration (AMD). The purpose of this study was to investigate the association of ARMS2/HTRA1 and CFH SNPs with early age-related maculopathy (ARM) in a Han Chinese cohort.<h4>Methods</h4>The cohort consisted of 315 unrelated subjects, including 158 patients wit ...[more]

PMID: 23687431

Similar Datasets

Project description:To examine if the genes encoding the pleckstrin homology domain-containing protein gene (PLEKHA1), hypothetical LOC387715/ARMS2 gene, and HtrA serine peptidase 1 gene (HTRA1) located on the long arm of chromosome 10 (10q26 region) confer risk for neovascular age-related macular degeneration (AMD) in an independent or interactive manner when controlling for complement factor H gene (CFH) genotype and smoking exposure.Retrospective matched-pair case-control study.Hospital clinic-based sample of 134 unrelated patients with neovascular AMD who have a sibling with normal maculae (268 subjects).Disease status was ascertained by at least 2 investigators by review of fundus photographs and/or fluorescein angiography according to the Age-Related Eye Disease Study grading scale. If necessary, a home retinal examination was performed (n = 6). A combination of direct sequencing and analysis of 8 highly polymorphic microsatellite markers was used to genotype 33 megabases of the 10q26 region on leukocyte DNA. Smoking history was obtained via a standardized questionnaire and measured in pack-years. The family-based association test, haplotype analysis, multiple conditional logistic regression, and linkage analysis were used to determine significant associations.Neovascular AMD status.Of the 23 variants we identified in the 10q26 region, 6 were significant. Four of the 6 were novel and included 2 genotypes that reduced risk of AMD. Many single-nucleotide polymorphisms (SNPs), including the previously reported variants rs10490924 (hypothetical LOC387715/ARMS2) and rs11200638 (HTRA1), defined 2 significant haplotypes associated with increased risk of neovascular AMD. The coding HTRA1 SNP rs2293870, not part of the significant haplotypes containing rs10490924 and rs11200638, showed as strong an association with increased susceptibility to neovascular AMD. Linkage analysis supported our findings of SNP association (P<10(-15)). No significant interactions were found between any of the SNPs in the 10q26 and smoking or between these SNPs and CFH genotype.Independent of CFH genotype or smoking history, an individual's risk of AMD could be increased or decreased, depending on their genotype or haplotype in the 10q26 region.

Project description:AIM:Age-related macular degeneration (AMD) is a multifactorial disease and a prevalent cause of visual impairment in developed countries. Many studies suggest that age-related maculopathy susceptibility 2 (ARMS2) is a second major susceptibility gene for AMD. At present, there is no functional information on this gene. Therefore, the purpose of the present study was to detect the expression of ARMS2 in retinal pigment epithelium (RPE) cells and to investigate the effect of ARMS2 on the phagocytosis function of RPE cells. METHODS:Immunofluorescence and reverse transcriptase PCR were used to demonstrate the presence and location of ARMS2 in ARPE-19 (human retinal pigment epithelial cell line, ATCC, catalog No.CRL-2302) cells. siRNA was used to knock down ARMS2 mRNA, and the effects of the knockdown on the phagocytosis function of the ARPE-19 cells were evaluated via Fluorescence Activated Cell Sorting (FACS). RESULTS:ARMS2 was present in ARPE-19 cells, localized in the cytosol of the perinuclear region. The expression of ARMS2 mRNA (messenger RNA) in ARPE-19 cells transfected with ARMS2-siRNA (small interfering RNA, 0.73±0.08) was decreased compared with normal cells (1.00±0.00) or with cells transfected with scrambled siRNA (0.95±0.13) (P<0.05). After incubation of RPE cells with a latex beads medium for 12, 18, or 24 hours, the fluorescence intensities were 38.04±1.02, 68.92±0.92, and 78.00±0.12 in the ARMS2-siRNA-transfected groups, respectively, and 77.98±5.43, 94.87±0.60, and 98.30±0.11 in the scrambled siRNA-transfected groups, respectively. The fluorescent intensities of the same time points in the two groups were compared using Student's t-test, and the p values were all less than 0.001 at the three different time points. CONCLUSION:There is endogenous expression of ARMS2 in ARPE-19 cells. ARMS2 plays a role in the phagocytosis function of RPE cells, and this role may be one of the mechanisms that participates in the development of AMD.

Dataset Information

No association of age-related maculopathy susceptibility protein 2/HtrA serine peptidase 1 or complement factor H polymorphisms with early age-related maculopathy in a Chinese cohort.

Publications

No association of age-related maculopathy susceptibility protein 2/HtrA serine peptidase 1 or complement factor H polymorphisms with early age-related maculopathy in a Chinese cohort.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets