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D6S265*15 marks a DRB1*15, DQB1*0602 haplotype associated with attenuated protection from type 1 diabetes mellitus.

Valdes, A M; Thomson, G; Graham, J; Zarghami, M; McNeney, B; Kockum, I; Smith, A; Lathrop, M; Steenkiste, A R and Dorman, J S, et al. (2005) In Diabetologia 48(12). p.2540-2543
Abstract
Aims/hypothesis: 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.

Methods: We defined alleles at eight microsatellite markers spanning the HLA region in a case-control cohort from Sweden.

Results: 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... (More)
Aims/hypothesis: 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.

Methods: We defined alleles at eight microsatellite markers spanning the HLA region in a case-control cohort from Sweden.

Results: 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), p<0.001].

Conclusions/interpretation: 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.

Electronic Supplementary Material: Supplementary material is available for this article at http://dx.doi.org/10.1007/s00125-005-0011-8 (Less)
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type
Contribution to journal
publication status
published
subject
keywords
D6S265, DQB1*0602, HLA-DQ antigens, IDDM, Type 1 diabetes mellitus
in
Diabetologia
volume
48
issue
12
pages
2540 - 2543
publisher
Springer Verlag
external identifiers
  • scopus:28444477379
ISSN
1432-0428
DOI
10.1007/s00125-005-0011-8
language
English
LU publication?
no
id
a486139d-1966-452f-88d8-8d3e6c9673f9 (old id 1133058)
date added to LUP
2008-06-25 14:24:52
date last changed
2017-07-23 03:55:20
@article{a486139d-1966-452f-88d8-8d3e6c9673f9,
  abstract     = {Aims/hypothesis: 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.<br/><br>
Methods: We defined alleles at eight microsatellite markers spanning the HLA region in a case-control cohort from Sweden.<br/><br>
Results: 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), p&lt;0.001].<br/><br>
Conclusions/interpretation: 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.<br/><br>
Electronic Supplementary Material: Supplementary material is available for this article at http://dx.doi.org/10.1007/s00125-005-0011-8},
  author       = {Valdes, A M and Thomson, G and Graham, J and Zarghami, M and McNeney, B and Kockum, I and Smith, A and Lathrop, M and Steenkiste, A R and Dorman, J S and Noble, J A and Hansen, J A and Pugliese, A and Lernmark, Åke and Diabetes Incidence in Sweden Study Group, Type 1 Diabetes Component of the 13th International Histocompatibility Working Group, Swedish Childhood Study Group,},
  issn         = {1432-0428},
  keyword      = {D6S265,DQB1*0602,HLA-DQ antigens,IDDM,Type 1 diabetes mellitus},
  language     = {eng},
  number       = {12},
  pages        = {2540--2543},
  publisher    = {Springer Verlag},
  series       = {Diabetologia},
  title        = {D6S265*15 marks a DRB1*15, DQB1*0602 haplotype associated with attenuated protection from type 1 diabetes mellitus.},
  url          = {http://dx.doi.org/10.1007/s00125-005-0011-8},
  volume       = {48},
  year         = {2005},
}