The Experts below are selected from a list of 78 Experts worldwide ranked by ideXlab platform
Gaetano R Barile - One of the best experts on this subject based on the ideXlab platform.
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variation in factor b bf and Complement Component 2 c2 genes is associated with age related macular degeneration
Nature Genetics, 2006Co-Authors: Bert Gold, Joanna E Merriam, Jana Zernant, Lisa S Hancox, Andrew J Taiber, Karen M Gehrs, Kevin Cramer, Julia Neel, Julie Bergeron, Gaetano R BarileAbstract:Variation in factor B ( BF ) and Complement Component 2 ( C2 ) genes is associated with age-related macular degeneration
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variation in factor b bf and Complement Component 2 c2 genes is associated with age related macular degeneration
Nature Genetics, 2006Co-Authors: Bert Gold, Joanna E Merriam, Jana Zernant, Lisa S Hancox, Andrew J Taiber, Karen M Gehrs, Kevin Cramer, Julia Neel, Julie Bergeron, Gaetano R BarileAbstract:Age-related macular degeneration (AMD) is the most common form of irreversible blindness in developed countries. Variants in the factor H gene (CFH, also known as HF1), which encodes a major inhibitor of the alternative Complement pathway, are associated with the risk for developing AMD. Here we test the hypothesis that variation in genes encoding other regulatory proteins of the same pathway is associated with AMD. We screened factor B (BF) and Complement Component 2 (C2) genes, located in the major histocompatibility complex class III region, for genetic variation in two independent cohorts comprising approximately 900 individuals with AMD and approximately 400 matched controls. Haplotype analyses identify a statistically significant common risk haplotype (H1) and two protective haplotypes. The L9H variant of BF and the E318D variant of C2 (H10), as well as a variant in intron 10 of C2 and the R32Q variant of BF (H7), confer a significantly reduced risk of AMD (odds ratio = 0.45 and 0.36, respectively). Combined analysis of the C2 and BF haplotypes and CFH variants shows that variation in the two loci can predict the clinical outcome in 74% of the affected individuals and 56% of the controls. These data expand and refine our understanding of the genetic risk for AMD.
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variation in factor b bf and Complement Component 2 c2 genes is associated with age related macular degeneration
Nature Genetics, 2006Co-Authors: Bert Gold, Joanna E Merriam, Jana Zernant, Lisa S Hancox, Andrew J Taiber, Karen M Gehrs, Kevin Cramer, Julia Neel, Julie Bergeron, Gaetano R BarileAbstract:Age-related macular degeneration (AMD) is the most common form of irreversible blindness in developed countries1,2. Variants in the factor H gene (CFH, also known as HF1), which encodes a major inhibitor of the alternative Complement pathway, are associated with the risk for developing AMD3,4,5,6,7,8. Here we test the hypothesis that variation in genes encoding other regulatory proteins of the same pathway is associated with AMD. We screened factor B (BF) and Complement Component 2 (C2) genes, located in the major histocompatibility complex class III region, for genetic variation in two independent cohorts comprising ∼900 individuals with AMD and ∼400 matched controls. Haplotype analyses identify a statistically significant common risk haplotype (H1) and two protective haplotypes. The L9H variant of BF and the E318D variant of C2 (H10), as well as a variant in intron 10 of C2 and the R32Q variant of BF (H7), confer a significantly reduced risk of AMD (odds ratio = 0.45 and 0.36, respectively). Combined analysis of the C2 and BF haplotypes and CFH variants shows that variation in the two loci can predict the clinical outcome in 74% of the affected individuals and 56% of the controls. These data expand and refine our understanding of the genetic risk for AMD.
Lisa S Hancox - One of the best experts on this subject based on the ideXlab platform.
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the pivotal role of the Complement system in aging and age related macular degeneration hypothesis re visited
Progress in Retinal and Eye Research, 2010Co-Authors: Don H Anderson, Lisa S Hancox, Monte J Radeke, Natasha B Gallo, E A Chapin, P T Johnson, Christy R Curletti, J N Ebright, Goldis Malek, Michael A HauserAbstract:During the past ten years, dramatic advances have been made in unraveling the biological bases of age-related macular degeneration (AMD), the most common cause of irreversible blindness in western populations. In that timeframe, two distinct lines of evidence emerged which implicated chronic local inflammation and activation of the Complement cascade in AMD pathogenesis. First, a number of Complement system proteins, Complement activators, and Complement regulatory proteins were identified as molecular constituents of drusen, the hallmark extracellular deposits associated with early AMD. Subsequently, genetic studies revealed highly significant statistical associations between AMD and variants of several Complement pathway-associated genes including: Complement factor H (CFH), Complement factor H-related 1 and 3 (CFHR1 and CFHR3), Complement factor B (CFB), Complement Component 2 (C2), and Complement Component 3 (C3). In this article, we revisit our original hypothesis that chronic local inflammatory and immune-mediated events at the level of Bruch's membrane play critical roles in drusen biogenesis and, by extension, in the pathobiology of AMD. Secondly, we report the results of a new screening for additional AMD-associated polymorphisms in a battery of 63 Complement-related genes. Third, we identify and characterize the local Complement system in the RPE-choroid complex - thus adding a new dimension of biological complexity to the role of the Complement system in ocular aging and AMD. Finally, we evaluate the most salient, recent evidence that bears directly on the role of Complement in AMD pathogenesis and progression. Collectively, these recent findings strongly re-affirm the importance of the Complement system in AMD. They lay the groundwork for further studies that may lead to the identification of a transcriptional disease signature of AMD, and hasten the development of new therapeutic approaches that will restore the Complement-modulating activity that appears to be compromised in genetically susceptible individuals.
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variation in factor b bf and Complement Component 2 c2 genes is associated with age related macular degeneration
Nature Genetics, 2006Co-Authors: Bert Gold, Joanna E Merriam, Jana Zernant, Lisa S Hancox, Andrew J Taiber, Karen M Gehrs, Kevin Cramer, Julia Neel, Julie Bergeron, Gaetano R BarileAbstract:Variation in factor B ( BF ) and Complement Component 2 ( C2 ) genes is associated with age-related macular degeneration
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variation in factor b bf and Complement Component 2 c2 genes is associated with age related macular degeneration
Nature Genetics, 2006Co-Authors: Bert Gold, Joanna E Merriam, Jana Zernant, Lisa S Hancox, Andrew J Taiber, Karen M Gehrs, Kevin Cramer, Julia Neel, Julie Bergeron, Gaetano R BarileAbstract:Age-related macular degeneration (AMD) is the most common form of irreversible blindness in developed countries. Variants in the factor H gene (CFH, also known as HF1), which encodes a major inhibitor of the alternative Complement pathway, are associated with the risk for developing AMD. Here we test the hypothesis that variation in genes encoding other regulatory proteins of the same pathway is associated with AMD. We screened factor B (BF) and Complement Component 2 (C2) genes, located in the major histocompatibility complex class III region, for genetic variation in two independent cohorts comprising approximately 900 individuals with AMD and approximately 400 matched controls. Haplotype analyses identify a statistically significant common risk haplotype (H1) and two protective haplotypes. The L9H variant of BF and the E318D variant of C2 (H10), as well as a variant in intron 10 of C2 and the R32Q variant of BF (H7), confer a significantly reduced risk of AMD (odds ratio = 0.45 and 0.36, respectively). Combined analysis of the C2 and BF haplotypes and CFH variants shows that variation in the two loci can predict the clinical outcome in 74% of the affected individuals and 56% of the controls. These data expand and refine our understanding of the genetic risk for AMD.
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variation in factor b bf and Complement Component 2 c2 genes is associated with age related macular degeneration
Nature Genetics, 2006Co-Authors: Bert Gold, Joanna E Merriam, Jana Zernant, Lisa S Hancox, Andrew J Taiber, Karen M Gehrs, Kevin Cramer, Julia Neel, Julie Bergeron, Gaetano R BarileAbstract:Age-related macular degeneration (AMD) is the most common form of irreversible blindness in developed countries1,2. Variants in the factor H gene (CFH, also known as HF1), which encodes a major inhibitor of the alternative Complement pathway, are associated with the risk for developing AMD3,4,5,6,7,8. Here we test the hypothesis that variation in genes encoding other regulatory proteins of the same pathway is associated with AMD. We screened factor B (BF) and Complement Component 2 (C2) genes, located in the major histocompatibility complex class III region, for genetic variation in two independent cohorts comprising ∼900 individuals with AMD and ∼400 matched controls. Haplotype analyses identify a statistically significant common risk haplotype (H1) and two protective haplotypes. The L9H variant of BF and the E318D variant of C2 (H10), as well as a variant in intron 10 of C2 and the R32Q variant of BF (H7), confer a significantly reduced risk of AMD (odds ratio = 0.45 and 0.36, respectively). Combined analysis of the C2 and BF haplotypes and CFH variants shows that variation in the two loci can predict the clinical outcome in 74% of the affected individuals and 56% of the controls. These data expand and refine our understanding of the genetic risk for AMD.
Bert Gold - One of the best experts on this subject based on the ideXlab platform.
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variation in factor b bf and Complement Component 2 c2 genes is associated with age related macular degeneration
Nature Genetics, 2006Co-Authors: Bert Gold, Joanna E Merriam, Jana Zernant, Lisa S Hancox, Andrew J Taiber, Karen M Gehrs, Kevin Cramer, Julia Neel, Julie Bergeron, Gaetano R BarileAbstract:Variation in factor B ( BF ) and Complement Component 2 ( C2 ) genes is associated with age-related macular degeneration
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variation in factor b bf and Complement Component 2 c2 genes is associated with age related macular degeneration
Nature Genetics, 2006Co-Authors: Bert Gold, Joanna E Merriam, Jana Zernant, Lisa S Hancox, Andrew J Taiber, Karen M Gehrs, Kevin Cramer, Julia Neel, Julie Bergeron, Gaetano R BarileAbstract:Age-related macular degeneration (AMD) is the most common form of irreversible blindness in developed countries. Variants in the factor H gene (CFH, also known as HF1), which encodes a major inhibitor of the alternative Complement pathway, are associated with the risk for developing AMD. Here we test the hypothesis that variation in genes encoding other regulatory proteins of the same pathway is associated with AMD. We screened factor B (BF) and Complement Component 2 (C2) genes, located in the major histocompatibility complex class III region, for genetic variation in two independent cohorts comprising approximately 900 individuals with AMD and approximately 400 matched controls. Haplotype analyses identify a statistically significant common risk haplotype (H1) and two protective haplotypes. The L9H variant of BF and the E318D variant of C2 (H10), as well as a variant in intron 10 of C2 and the R32Q variant of BF (H7), confer a significantly reduced risk of AMD (odds ratio = 0.45 and 0.36, respectively). Combined analysis of the C2 and BF haplotypes and CFH variants shows that variation in the two loci can predict the clinical outcome in 74% of the affected individuals and 56% of the controls. These data expand and refine our understanding of the genetic risk for AMD.
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variation in factor b bf and Complement Component 2 c2 genes is associated with age related macular degeneration
Nature Genetics, 2006Co-Authors: Bert Gold, Joanna E Merriam, Jana Zernant, Lisa S Hancox, Andrew J Taiber, Karen M Gehrs, Kevin Cramer, Julia Neel, Julie Bergeron, Gaetano R BarileAbstract:Age-related macular degeneration (AMD) is the most common form of irreversible blindness in developed countries1,2. Variants in the factor H gene (CFH, also known as HF1), which encodes a major inhibitor of the alternative Complement pathway, are associated with the risk for developing AMD3,4,5,6,7,8. Here we test the hypothesis that variation in genes encoding other regulatory proteins of the same pathway is associated with AMD. We screened factor B (BF) and Complement Component 2 (C2) genes, located in the major histocompatibility complex class III region, for genetic variation in two independent cohorts comprising ∼900 individuals with AMD and ∼400 matched controls. Haplotype analyses identify a statistically significant common risk haplotype (H1) and two protective haplotypes. The L9H variant of BF and the E318D variant of C2 (H10), as well as a variant in intron 10 of C2 and the R32Q variant of BF (H7), confer a significantly reduced risk of AMD (odds ratio = 0.45 and 0.36, respectively). Combined analysis of the C2 and BF haplotypes and CFH variants shows that variation in the two loci can predict the clinical outcome in 74% of the affected individuals and 56% of the controls. These data expand and refine our understanding of the genetic risk for AMD.
Yoon Jun Kim - One of the best experts on this subject based on the ideXlab platform.
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genetic association of Complement Component 2 variants with chronic hepatitis b in a korean population
Liver International, 2018Co-Authors: Suhg Namgoong, Joong Gon Shin, Hyun Sub Cheong, Lyoung Hyo Kim, Ji On Kim, Jung Yeon Seo, Hyoung Doo Shin, Yoon Jun KimAbstract:BACKGROUND & AIMS Numerous single nucleotide polymorphisms associated with an increased risk of liver diseases, chronic hepatitis B and chronic hepatitis B-related hepatocellular carcinoma have been identified. In this study, we scrutinized the genetic effects of C2 variants, which were conflicting in previous results, on the risk of chronic hepatitis B in a Korean population. METHODS We genotyped 22 common C2 genetic variants of 977 chronic hepatitis B cases including 302 chronic hepatitis B-related hepatocellular carcinoma cases and 785 population controls. Statistical analysis was performed to examine the effects of genotype on the risk of chronic hepatitis B and chronic hepatitis B-related hepatocellular carcinoma. RESULTS Logistic regression analyses showed that six C2 single nucleotide polymorphisms had significant associations with the risk of chronic hepatitis B and chronic hepatitis B-related hepatocellular carcinoma among the Korean subjects. Stepwise analysis revealed that causal markers (rs9267665 and rs10947223) were identified among the C2 variants (stepwise P = 3.32 × 10-9 and 2.04 × 10-5 respectively). In further conditional analysis with previous chronic hepatitis B-associated loci, these two single nucleotide polymorphisms were independently associated with the risk of chronic hepatitis B. In addition, we investigated the ability of genetic risk scores combining 12 multi-chronic hepatitis B loci to predict the risk of chronic hepatitis B. Individuals with higher genetic risk scores showed increased risk for chronic hepatitis B. CONCLUSIONS Our results suggested that the C2 gene might be a susceptibility locus for chronic hepatitis B in Korean populations. The cumulative genetic effects may contribute to future etiological explanations for chronic hepatitis B.
Johanna M Seddon - One of the best experts on this subject based on the ideXlab platform.
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dietary folate b vitamins genetic susceptibility and progression to advanced nonexudative age related macular degeneration with geographic atrophy a prospective cohort study
The American Journal of Clinical Nutrition, 2016Co-Authors: Benedicte M J Merle, Rachel E Silver, Bernard Rosner, Johanna M SeddonAbstract:BACKGROUND: There is growing evidence of the importance of nutrition in age-related macular degeneration (AMD), but few studies have explored associations with folate and B vitamins. No effective therapeutic strategy for geographic atrophy (GA) is available, and prevention could be of great value. OBJECTIVE: We investigated associations between dietary folate, B vitamins, and progression to GA and whether these associations might be modified by genetic susceptibility. DESIGN: Among 2525 subjects (4663 eyes) in the Age-Related Eye Disease Study, 405 subjects (528 eyes) progressed to GA over 13 y. Folate and B vitamins were log transformed and calorie adjusted separately for men and women. Ten loci in 7 AMD genes [Complement factor H, age-related maculopathy susceptibility 2/high-temperature requirement A serine peptidase 1, Complement Component 2, Complement Component 3, Complement factor B, collagen type VIII α 1, and RAD51 paralog B] were examined. Survival analysis was used to assess associations between incident GA and dietary intake of folate and B vitamins. Interaction effects between these nutrients and genetic variation on AMD risk were also evaluated. Subjects with at least one eye free of advanced AMD at baseline were included in these analyses. RESULTS: There was a reduced risk of progression to GA with increasing intake of thiamin, riboflavin, and folate after adjusting for age, sex, and total energy intake (P-trend = 0.01, 0.03, and 0.001, respectively). After adjustment for demographic, behavioral, ocular, and genetic covariates, trends remained statistically significant for folate (P-trend = 0.007) and were borderline for thiamin (P-trend = 0.05). Riboflavin did not retain statistical significance (P-trend = 0.20). Folate was significantly associated with lower risk of incident GA among subjects homozygous for the Complement Component 3 (C3) R102G rs2230199 nonrisk genotype (CC) (HR = 0.43; 95% CI: 0.27, 0.70; P = 0.0005) but not subjects carrying the risk allele (G) (P = 0.76). Neither folate nor any B vitamin was significantly associated with neovascular AMD. CONCLUSIONS: High folate intake was associated with a reduced risk of progression to GA. This relation could be modified by genetic susceptibility, particularly related to the C3 genotype. This trial was registered at clinicaltrials.gov as NCT00594672.
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adherence to a mediterranean diet genetic susceptibility and progression to advanced macular degeneration a prospective cohort study
The American Journal of Clinical Nutrition, 2015Co-Authors: Benedicte M J Merle, Rachel E Silver, Bernard Rosner, Johanna M SeddonAbstract:Background: Adherence to a Mediterranean-type diet is linked to a lower risk of mortality and chronic disease, but the association with the progression of age-related macular degeneration (AMD) and genetic susceptibility is unknown. Objective: We examined the association of adherence to the Mediterranean diet and genetic susceptibility with progression to advanced AMD. Design: Among 2525 subjects in the AREDS (Age-Related Eye Disease Study), 1028 eyes progressed to advanced AMD over 13 y. Baseline data for demographic and behavioral covariates were collected by using questionnaires. Dietary data were collected from food-frequency questionnaires. The alternate Mediterranean diet (aMeDi) score (range: 0–9) was constructed from individual intakes of vegetables, fruit, legumes, whole grains, nuts, fish, red and processed meats, alcohol, and the ratio of monounsaturated to saturated fats. Ten genetic loci in 7 genes [Complement factor H (CFH), age-related maculopathy susceptibility 2/high-temperature requirement A serine peptidase 1 (ARMS2/HTRA1), Complement Component 2 (C2), Complement factor B (CFB), Complement Component 3 (C3), collagen type VIII α 1 (COL8A1), and RAD51 paralog B (RAD51B)] were examined. Survival analysis was used to assess individual eyes for associations between incident AMD and aMeDi score, as well as interaction effects between aMeDi score and genetic variation on risk of AMD. Results: A high aMeDi score (score of 6–9) was significantly associated with a reduced risk of progression to advanced AMD after adjustment for demographic, behavioral, ocular, and genetic covariates (HR: 0.74; 95% CI: 0.61, 0.91; P-trend = 0.007). The aMeDi score was significantly associated with a lower risk of incident advanced AMD among subjects carrying the CFH Y402H nonrisk (T) allele (P-trend = 0.0004, P-interaction = 0.04). The aMeDi score was not associated with AMD among subjects who were homozygous for the risk (C) allele. Conclusion: Higher adherence to a Mediterranean diet was associated with reduced risk of progression to advanced AMD, which may be modified by genetic susceptibility. This trial was registered at clinicaltrials.gov as NCT00594672.