Dataset Information

Lens status influences the association between CFH polymorphisms and age-related macular degeneration: findings from two population-based studies in Singapore.

ABSTRACT:

Aims

To determine the differential effects of genetic polymorphism in CFH and ARMS2 on risk of age-related macular degeneration (AMD) between phakic vs. pseudophakic/aphakic eyes.

Methods

9,529 eyes of 4,918 participants from the Singapore Malay Eye Study and Singapore Indian Eye Study were analyzed. Participants had detailed eye examinations, including slit-lamp examinations and dilated fundus photography. AMD grading was performed according to the Wisconsin age-related maculopathy grading system. Lens status was defined. Single nucleotide polymorphisms (SNPs) rs10801555 (Y402H) within CFH and rs3750847 in ARMS2 were assessed. The main outcome measure was early AMD or any AMD.

Results

No significant associations between the CFH Y402H genotypes and early AMD were found in phakic individuals. In contrast, among pseudophakic/aphakic individuals, the CFH Y402H risk genotypes were significantly associated with higher odds of early AMD, with an OR of 1.57 (95% CI: 1.07-2.29) for GA genotype and 2.40 (95% CI: 1.25-4.61) for AA genotype, compared to those with GG genotype. There was significant interaction between pseudophakic/aphakic status and CFH Y402H variant on risk of early AMD (p = 0.037), adjusting for age, gender, and the first 5 genetic principal components. No significant interaction was found between lens status and ARMS2 rs3750847.

Conclusions

CFH genetic polymorphism and pseudophakic/aphakic status may have a potential synergistic effect on early AMD, suggesting roles for the complement system and related pathways in the pathogenesis of AMD in eyes after cataract surgery.

SUBMITTER: Wong CW

PROVIDER: S-EPMC4364964 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Lens status influences the association between CFH polymorphisms and age-related macular degeneration: findings from two population-based studies in Singapore.

Wong Chee Wai CW Liao Jiemin J Cheung Gemmy C GC Khor Chiea Chuen CC Vithana Eranga N EN Wang Jie Jin JJ Mitchell Paul P Aung Tin T Wong Tien Y TY Cheng Ching-Yu CY

PloS one 20150318 3

<h4>Aims</h4>To determine the differential effects of genetic polymorphism in CFH and ARMS2 on risk of age-related macular degeneration (AMD) between phakic vs. pseudophakic/aphakic eyes.<h4>Methods</h4>9,529 eyes of 4,918 participants from the Singapore Malay Eye Study and Singapore Indian Eye Study were analyzed. Participants had detailed eye examinations, including slit-lamp examinations and dilated fundus photography. AMD grading was performed according to the Wisconsin age-related maculopat ...[more]

PMID: 25786237

Similar Datasets

Project description:PurposeVariants in complement factor H (CFH), the hypothetical LOC387715, and the high-temperature requirement A-1 (HTRA1) genes have been reported to be associated with age-related macular degeneration (AMD). The purpose of this study was to investigate the association of reported common single-nucleotide polymorphisms (SNPs) in CFH, LOC387715, and HTRA1 with exudative AMD in a northern Chinese population.MethodsA cohort of 121 unrelated patients with exudative AMD and 132 control subjects were enrolled in this study. Genomic DNA was extracted from blood leukocytes. Genotyping for SNPs rs1061170:T>C in CFH (Y402H), rs10490924:G>T in LOC387715 (A69S), and rs11200638:G>A in the promoter of HTRA1 was performed using a polymerase chain reaction (PCR) method followed by allele-specific restriction enzyme digestion and direct sequencing.ResultsThe Y402H variant in CFH was not associated with exudative AMD in our study population. Frequencies of Y402H was 10.3% in AMD cases and 8.0% in controls (p=0.353). Significant associations were detected for exudative AMD with SNPs rs10490924:G>T in LOC387715 (A69S), and rs11200638:G>A in the promoter of HTRA1. The risk T-allele frequency of rs10490924 in LOC387715 was 64.9% in cases versus 43.2% in controls (p<0.001). The odds ratio for risk of AMD was 1.56 (95% CI; 0.80-3.03) for the GT genotype and 5.45 (95% CI; 2.59-11.49) for the TT genotype. The A allele frequency of rs11200638 in the HTRA1 promoter was 67.8% in cases versus 42.4% in controls (p<0.001). The odds ratio was 2.75 (95% CI; 1.34-5.64) for the GA genotype and 7.90 (95% CI; 3.61-17.26) for the AA genotype. An odds ratio of 7.94 (95% CI; 3.49-18.04) was obtained for carriers with both TT genotype in LOC387715 and AA genotype in the HTRA1 promoter.ConclusionsOur data suggest that the LOC387715 and HTRA1 polymorphisms are associated with a higher risk of exudative AMD in northern Chinese. We found no association of CFH Y402H with exudative AMD. The low frequency of CFH Y402H variant was further confirmed in this study population.

Project description:BACKGROUND: Age-related macular degeneration (AMD) is the major cause of blindness in the elderly. Those with the neovascular end-stage of disease have irreversible loss of central vision. AMD is a complex disorder in which genetic and environmental factors play a role. Polymorphisms in the complement factor H (CFH) gene, LOC387715, and the HTRA1 promoter are strongly associated with AMD. Smoking also contributes to the etiology. We aimed to provide a model of disease risk based on these factors. METHODS AND FINDINGS: We genotyped polymorphisms in CFH and LOC387715/HTRA1 in a case-control study of 401 patients with neovascular AMD and 266 controls without signs of disease, and used the data to produce genetic risk scores for the European-descent population based on haplotypes at these loci and smoking history. CFH and LOC387715/HTRA1 haplotypes and smoking status exerted large effects on AMD susceptibility, enabling risk scores to be generated with appropriate weighting of these three factors. Five common haplotypes of CFH conferred a range of odds ratios (ORs) per copy from 1 to 4.17. Most of the effect of LOC387715/HTRA1 was mediated through one detrimental haplotype (carriage of one copy: OR 2.83; 95% confidence interval [CI] 1.91-4.20), with homozygotes being at particularly high risk (OR 32.83; 95% CI 12.53-86.07). Patients with neovascular macular degeneration had considerably higher scores than those without disease, and risk of blinding AMD rose to 15.5% in the tenth of the population with highest predicted risk. CONCLUSIONS: An individual's risk of developing AMD in old age can be predicted by combining haplotype data with smoking status. Until there is effective treatment for AMD, encouragement to avoid smoking in those at high genetic risk may be the best option. We estimate that total absence of smoking would have reduced the prevalence of severe AMD by 33%. Unless smoking habits change or preventative treatment becomes available, the prevalence of AMD will rise as a consequence of the increasing longevity of the population.

Project description:PurposeThe purpose of this study is to evaluate the effect of complement factor H (CFH) Y402H CC and TT polymorphisms on treatment response to intravitreal ranibizumab injection in patients with wet age-related macular degeneration (AMD).MethodsOne hundred ninety-three patients with choroidal neovascularization (CNV) secondary to AMD who were monitored for at least 6 months of follow-up, and with at least three ranibizumab injections, were included in the study. At the final examination, an increase in visual acuity (VA) of five letters or more compared to the initial VA was regarded as a good response, and a decrease in VA of five letters or more compared to the initial VA was evaluated as a poor response. A genetic examination was performed with a PCR melting curve analysis. In the statistical evaluation, SPSS version 18 software was used.ResultsThe mean age of the patients was 71.01 (55-86) years, the mean follow-up was 13.34 (6-36) months, and the mean number of injections was 4.02 (3-15). There were 96 patients in the good response group (Group 1) and 97 patients in the poor response group (Group 2). The initial VA in Group 1 was 41.34 (10-64) letters, the initial central macular thickness (CMT) was 213.40 (126-494) µm, and the initial lesion width was 3760 (1430-6430) µm. The initial VA in Group 2 was 52.89 (26-82) letters, the initial CMT was 257.60 (115-882) µm, and the initial lesion width was 4460 (1000-7650) µm. There was no statistically significant difference between the two groups in terms of the initial VA and CMT (p=0.094, p=0.083). However, there was a statistically significant difference between the groups in the width of the initial lesion (p=0.003). In Group 1, 15 CC, 30 TT, and 51 TC alleles were found, and in Group 2, 49 CC, two TT, and 46 TC alleles were found, and the distribution was significantly different between the two groups (p=0.012). The change in the distribution of genotypes was not associated with either the lesion size or VA (p=0.841). Fibrosis developed in 12 patients who were all poor responders.ConclusionsCFH Y402H CC accompanied a poor response, and TT accompanied a good response in this series of patients with AMD undergoing ranibizumab therapy.

Dataset Information

Lens status influences the association between CFH polymorphisms and age-related macular degeneration: findings from two population-based studies in Singapore.

Aims

Methods

Results

Conclusions

Publications

Lens status influences the association between CFH polymorphisms and age-related macular degeneration: findings from two population-based studies in Singapore.

Similar Datasets

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