Abstract:Age-related macular degeneration (AMD) risk variants in the complement system point to the important role of immune response and inflammation in the pathogenesis of AMD. Although the human leukocyte antigen (HLA) region has a central role in regulating immune response, previous studies of genetic variation in HLA genes and AMD have been limited by sample size or incomplete coverage of the HLA region by first-generation genotyping arrays and imputation panels. Here, we conducted a large-scale HLA fine-mapping s… Show more
“…Figure 4 contains information on HLA-DQB1 locus SNPs plotted for association with AAMD. In support of these findings, HLA-DQB1 has been strongly implicated in AMD pathogenesis through a recent HLA fine-mapping study in >25,000 people [21] this work extended findings from two reports published HLA-DQB1 rs1770 6.64E-11 Decrease miRNAs were selected from differential expression studies in retina [13,16] and vitreous [19]. miRSNPs were identified with the miRanda 3.3 algorithm in the MirSNP database (bioinfo.bjmu.edu.cn/mirsnp/).…”
Section: Linking Mirnas To Aamd Pathogenesis and Pathophysiology: Aamsupporting
confidence: 52%
“…Jorgensen et al [21] present an overview on the biologic plausibility of MHC relationships in AMD pathogenesis, suggesting that progression to AAMD may be the result of dysregulated immune and inflammatory response to RPE damage associated with alterations in MHC and the complement systems (also discussed in Lukiw et al [16]). These authors cite evidence indicating increased HLA class II immunoreactivity exists in retinal specimens of people with AMD [22] and that HLA class II antigens are constituents of drusen [23].…”
Section: Linking Mirnas To Aamd Pathogenesis and Pathophysiology: Aammentioning
Advanced age-related macular degeneration (AAMD) is a complex sight-threating disease of public health significance. Micro RNAs (miRNAs) have been proposed as biomarkers for AAMD.
“…Figure 4 contains information on HLA-DQB1 locus SNPs plotted for association with AAMD. In support of these findings, HLA-DQB1 has been strongly implicated in AMD pathogenesis through a recent HLA fine-mapping study in >25,000 people [21] this work extended findings from two reports published HLA-DQB1 rs1770 6.64E-11 Decrease miRNAs were selected from differential expression studies in retina [13,16] and vitreous [19]. miRSNPs were identified with the miRanda 3.3 algorithm in the MirSNP database (bioinfo.bjmu.edu.cn/mirsnp/).…”
Section: Linking Mirnas To Aamd Pathogenesis and Pathophysiology: Aamsupporting
confidence: 52%
“…Jorgensen et al [21] present an overview on the biologic plausibility of MHC relationships in AMD pathogenesis, suggesting that progression to AAMD may be the result of dysregulated immune and inflammatory response to RPE damage associated with alterations in MHC and the complement systems (also discussed in Lukiw et al [16]). These authors cite evidence indicating increased HLA class II immunoreactivity exists in retinal specimens of people with AMD [22] and that HLA class II antigens are constituents of drusen [23].…”
Section: Linking Mirnas To Aamd Pathogenesis and Pathophysiology: Aammentioning
Advanced age-related macular degeneration (AAMD) is a complex sight-threating disease of public health significance. Micro RNAs (miRNAs) have been proposed as biomarkers for AAMD.
“…We find that SNP2HLA generated high confidence imputation at one- and two-field resolution which was validated by SSP-based direct HLA typing for 5 loci. Imputation of HLA alleles and amino acid polymorphisms using SNP2HLA has been successfully implemented for genetic studies of associations in a range of traits [44], [45], [46], [47], [48].…”
This study aimed to establish the occurrence and frequency of HLA alleles and haplotypes for a healthy British Caucasian population bioresource from Oxfordshire. We present the results of imputation from HLA SNP genotyping data using SNP2HLA for 5553 individuals from Oxford Biobank, defining one- and two-field alleles together with amino acid polymorphisms. We show that this achieves a high level of accuracy with validation using sequence-specific primer amplification PCR. We define six- and eight-locus HLA haplotypes for this population by Bayesian methods implemented using PHASE. We determine patterns of linkage disequilibrium and recombination for these individuals involving classical HLA loci and show how analysis within a haplotype block structure may be more tractable for imputed data. Our findings contribute to knowledge of HLA diversity in healthy populations and further validate future large-scale use of HLA imputation as an informative approach in population bioresources.
“…Because of the critical role of HLA-G and the strict conservation of the gene, it is perhaps not surprising that we did not find major differences on a genetic level. A comprehensive fine-mapping study by Jorgensen et al 33 examined HLA risk alleles that might be associated with AMD. An FIGURE 1 HLA-G gene expression in the retinal pigment epithelium (RPE)/choroid in donor eyes.…”
The study aims to determine if genetic polymorphisms in the human leukocyte antigen (HLA)-G gene are associated with age-related macular degeneration (AMD). HLA-G is important for immunological tolerance, and it is also known to have angiogenic effects. Polymorphisms in the 5'-upstream regulatory region (URR) and 3'-untranslated region (UTR) of HLA-G have been associated with a number of diseases, especially with respect to a 14 bp insertion/deletion (ins/del) polymorphism in the 3'UTR. Full gene sequencing was performed on a cohort of 146 AMD patients and 63 healthy controls aged 60 years or older and HLA-G haplotypes were determined. Analyses were performed on a publicly available gene expression dataset from the NCBI GEO database (accession number GSE29801) from which expression data for HLA-G, -C and -A were extracted. Analysis of the GEO dataset showed that both HLA-G and -C was expressed in the back of the eye and that expression was upregulated in the macular area of AMD. No differences were observed between patients and controls when analysing the distribution of haplotypes in the HLA-G promoter, coding region, 3'UTR or the 14 bp ins/del polymorphism of the 3'UTR. The increased expression of HLA-G in the macula of AMD patients indicates a role of HLA-G in the micro environment as part of the AMD pathogenesis. This is supported by the expression of HLA-C, which has previously been shown to play a role in AMD. The HLA-G haplotype distribution did not display any differences between AMD patients and controls. This article is protected by copyright. All rights reserved.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.