Linkage Analysis of Genomic Regions Contributing to the Expression of Type 1 Diabetes Microvascular Complications and Interaction with HLA
We conducted linkage analysis to follow up earlier work on microvascular complications of type 1 diabetes (T1D). We analyzed 415 families (2,008 individuals) previously genotyped for 402 SNP markers spanning chromosome 6. We did linkage analysis for the phenotypes of retinopathy and nephropathy. For...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2015/694107 |
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| author | Ettie M. Lipner Yaron Tomer Janelle A. Noble Maria C. Monti John T. Lonsdale Barbara Corso David A. Greenberg |
| author_facet | Ettie M. Lipner Yaron Tomer Janelle A. Noble Maria C. Monti John T. Lonsdale Barbara Corso David A. Greenberg |
| author_sort | Ettie M. Lipner |
| collection | DOAJ |
| description | We conducted linkage analysis to follow up earlier work on microvascular complications of type 1 diabetes (T1D). We analyzed 415 families (2,008 individuals) previously genotyped for 402 SNP markers spanning chromosome 6. We did linkage analysis for the phenotypes of retinopathy and nephropathy. For retinopathy, two linkage peaks were mapped: one located at the HLA region and another novel locus telomeric to HLA. For nephropathy, a linkage peak centromeric to HLA was mapped, but the linkage peak telomeric to HLA seen in retinopathy was absent. Because of the strong association of T1D with DRB1*03:01 and DRB1*04:01, we stratified our analyses based on families whose probands were positive for DRB1*03:01 or DRB1*04:01. When analyzing the DRB1*03:01-positive retinopathy families, in addition to the novel telomeric locus, one centromeric to HLA was identified at the same location as the nephropathy peak. When we stratified on DRB1*04:01-positive families, the HLA telomeric peak strengthened but the centromeric peak disappeared. Our findings showed that HLA and non-HLA loci on chromosome 6 are involved in T1D complications’ expression. While the HLA region is a major contributor to the expression of T1D, our results suggest an interaction between specific HLA alleles and other loci that influence complications’ expression. |
| format | Article |
| id | doaj-art-5fdfc2160a7a43afab827bfead0c690f |
| institution | OA Journals |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-5fdfc2160a7a43afab827bfead0c690f2025-08-20T02:24:00ZengWileyJournal of Diabetes Research2314-67452314-67532015-01-01201510.1155/2015/694107694107Linkage Analysis of Genomic Regions Contributing to the Expression of Type 1 Diabetes Microvascular Complications and Interaction with HLAEttie M. Lipner0Yaron Tomer1Janelle A. Noble2Maria C. Monti3John T. Lonsdale4Barbara Corso5David A. Greenberg6Integrated Center for Genes, Environment and Health, National Jewish Health, Denver, CO 80206, USADepartment of Medicine, Mount Sinai Medical Center, New York, NY 10013, USAChildren’s Hospital Oakland Research Institute, Oakland, CA 94702, USANational Research Council, Neuroscience Institute, 35128 Padova, ItalyNational Disease Research Interchange, Philadelphia, PA 19103, USANational Research Council, Neuroscience Institute, 35128 Padova, ItalyBattelle Center for Mathematical Medicine, Nationwide Children’s Hospital, Columbus, OH 43215, USAWe conducted linkage analysis to follow up earlier work on microvascular complications of type 1 diabetes (T1D). We analyzed 415 families (2,008 individuals) previously genotyped for 402 SNP markers spanning chromosome 6. We did linkage analysis for the phenotypes of retinopathy and nephropathy. For retinopathy, two linkage peaks were mapped: one located at the HLA region and another novel locus telomeric to HLA. For nephropathy, a linkage peak centromeric to HLA was mapped, but the linkage peak telomeric to HLA seen in retinopathy was absent. Because of the strong association of T1D with DRB1*03:01 and DRB1*04:01, we stratified our analyses based on families whose probands were positive for DRB1*03:01 or DRB1*04:01. When analyzing the DRB1*03:01-positive retinopathy families, in addition to the novel telomeric locus, one centromeric to HLA was identified at the same location as the nephropathy peak. When we stratified on DRB1*04:01-positive families, the HLA telomeric peak strengthened but the centromeric peak disappeared. Our findings showed that HLA and non-HLA loci on chromosome 6 are involved in T1D complications’ expression. While the HLA region is a major contributor to the expression of T1D, our results suggest an interaction between specific HLA alleles and other loci that influence complications’ expression.http://dx.doi.org/10.1155/2015/694107 |
| spellingShingle | Ettie M. Lipner Yaron Tomer Janelle A. Noble Maria C. Monti John T. Lonsdale Barbara Corso David A. Greenberg Linkage Analysis of Genomic Regions Contributing to the Expression of Type 1 Diabetes Microvascular Complications and Interaction with HLA Journal of Diabetes Research |
| title | Linkage Analysis of Genomic Regions Contributing to the Expression of Type 1 Diabetes Microvascular Complications and Interaction with HLA |
| title_full | Linkage Analysis of Genomic Regions Contributing to the Expression of Type 1 Diabetes Microvascular Complications and Interaction with HLA |
| title_fullStr | Linkage Analysis of Genomic Regions Contributing to the Expression of Type 1 Diabetes Microvascular Complications and Interaction with HLA |
| title_full_unstemmed | Linkage Analysis of Genomic Regions Contributing to the Expression of Type 1 Diabetes Microvascular Complications and Interaction with HLA |
| title_short | Linkage Analysis of Genomic Regions Contributing to the Expression of Type 1 Diabetes Microvascular Complications and Interaction with HLA |
| title_sort | linkage analysis of genomic regions contributing to the expression of type 1 diabetes microvascular complications and interaction with hla |
| url | http://dx.doi.org/10.1155/2015/694107 |
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