D6S265*15 marks a DRB1*15, DQB1*0602 haplotype associated with attenuated protection from type 1 diabetes mellitus
| Autor: | Jinko Graham, Mark Lathrop, Brad McNeney, J. S. Dorman, Ingrid Kockum, Ann R. Steenkiste, G Thomson, Ana M. Valdes, J A Hansen, M Zarghami, Anajane G. Smith, Alberto Pugliese, Janelle A. Noble, Åke Lernmark |
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| Rok vydání: | 2005 |
| Předmět: |
Adult
Male Risk endocrine system diseases Endocrinology Diabetes and Metabolism Human leukocyte antigen Cohort Studies Predictive Value of Tests HLA-DQ Antigens Diabetes mellitus Odds Ratio Internal Medicine medicine HLA-DQ beta-Chains Humans Genetic Predisposition to Disease Allele Alleles Sweden Type 1 diabetes Membrane Glycoproteins HLA-DQ Antigen business.industry Haplotype Case-control study Chromosome Mapping HLA-DR Antigens Odds ratio Middle Aged medicine.disease Diabetes Mellitus Type 1 Haplotypes Case-Control Studies Immunology Female business HLA-DRB1 Chains Microsatellite Repeats |
| Zdroj: | Diabetologia. 48:2540-2543 |
| ISSN: | 1432-0428 0012-186X |
| DOI: | 10.1007/s00125-005-0011-8 |
| Popis: | The HLA class II DQB1*0602 allele confers strong dominant protection against type 1 diabetes but protection is not absolute. The aim of this study was to identify markers within the HLA region that differentiate DQB1*0602 haplotypes and show different associations with disease risk.We defined alleles at eight microsatellite markers spanning the HLA region in a case-control cohort from Sweden.We found that allele 15 at marker D6S265 (109 kb centromeric of HLA-A) was over-represented among patients carrying DRB1*15, DQB1*0602. A detailed haplotype analysis showed that DRB1*15, DQB1*0602 haplotypes carrying D6S265*15 have a ten-fold higher odds ratio (OR) than those carrying other alleles and thus confer reduced protection [OR D6S265*15=0.186 (95% CI 0.074, 0.472) vs OR D6S265*15-=0.017 (95% CI 0.005, 0.062), p0.001].Our data support the existence of a locus that modifies the protective effect associated with DQB1*0602. Typing for allele D6S265*15 can identify a less protective DQB1*0602 haplotype, thereby allowing a more accurate prediction of type 1 diabetes risk. |
| Databáze: | OpenAIRE |
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