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

A. M. Valdes; G. Thomson; J. Graham; M. Zarghami; B. McNeney; I. Kockum; A. Smith; M. Lathrop; A. R. Steenkiste; J. S. Dorman; J. A. Noble; J. A. Hansen; A. Pugliese; Å Lernmark

doi:10.1007/s00125-005-0011-8

D6S26515 marks a DRB115, DQB1*0602 haplotype associated with attenuated protection from type 1 diabetes mellitus

A. M. Valdes, G. Thomson, J. Graham, M. Zarghami, B. McNeney, I. Kockum, A. Smith, M. Lathrop, A. R. Steenkiste, J. S. Dorman, J. A. Noble, J. A. Hansen, A. Pugliese, Å Lernmark

Medicine

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

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 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.

Original language	English (US)
Pages (from-to)	2540-2543
Number of pages	4
Journal	Diabetologia
Volume	48
Issue number	12
DOIs	https://doi.org/10.1007/s00125-005-0011-8
State	Published - Dec 2005

Keywords

0602
D6S265
DQB1
HLA-DQ antigens
IDDM
Type 1 diabetes mellitus

ASJC Scopus subject areas

Internal Medicine
Endocrinology, Diabetes and Metabolism

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Valdes, A. M., Thomson, G., Graham, J., Zarghami, M., McNeney, B., Kockum, I., Smith, A., Lathrop, M., Steenkiste, A. R., Dorman, J. S., Noble, J. A., Hansen, J. A., Pugliese, A., & Lernmark, Å. (2005). D6S265*15 marks a DRB1*15, DQB1*0602 haplotype associated with attenuated protection from type 1 diabetes mellitus. Diabetologia, 48(12), 2540-2543. https://doi.org/10.1007/s00125-005-0011-8

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.; Dorman, J. S.; Noble, J. A.; Hansen, J. A.; Pugliese, A.; Lernmark, Å.

In: Diabetologia, Vol. 48, No. 12, 12.2005, p. 2540-2543.

Research output: Contribution to journal › Article › peer-review

Valdes, AM, Thomson, G, Graham, J, Zarghami, M, McNeney, B, Kockum, I, Smith, A, Lathrop, M, Steenkiste, AR, Dorman, JS, Noble, JA, Hansen, JA, Pugliese, A & Lernmark, Å 2005, 'D6S265*15 marks a DRB1*15, DQB1*0602 haplotype associated with attenuated protection from type 1 diabetes mellitus', Diabetologia, vol. 48, no. 12, pp. 2540-2543. https://doi.org/10.1007/s00125-005-0011-8

Valdes, A. M. ; Thomson, G. ; Graham, J. ; Zarghami, M. ; McNeney, B. ; Kockum, I. ; Smith, A. ; Lathrop, M. ; Steenkiste, A. R. ; Dorman, J. S. ; Noble, J. A. ; Hansen, J. A. ; Pugliese, A. ; Lernmark, Å. / D6S265*15 marks a DRB1*15, DQB1*0602 haplotype associated with attenuated protection from type 1 diabetes mellitus. In: Diabetologia. 2005 ; Vol. 48, No. 12. pp. 2540-2543.

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

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 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.",

keywords = "0602, D6S265, DQB1, HLA-DQ antigens, IDDM, Type 1 diabetes mellitus",

author = "Valdes, {A. M.} and G. Thomson and J. Graham and M. Zarghami and B. McNeney and I. Kockum and A. Smith and M. Lathrop and Steenkiste, {A. R.} and Dorman, {J. S.} and Noble, {J. A.} and Hansen, {J. A.} and A. Pugliese and {\AA} Lernmark",

note = "Funding Information: Acknowledgements This work was supported by grants from the National Institutes of Health (NIH AI-49213 supporting G. Thomson, A. M. Valdes, {\AA}. Lernmark, J. A. Hansen, A. Pugliese, J. S. Dorman, A. R. Steenkiste, A. Smith) and grants DK-26910 and DK-53004 to {\AA}. Lernmark. It was also supported by the American Diabetes Association (grant to A. Pugliese) and the Juvenile Diabetes Research Foundation (grant to {\AA}. Lernmark).",

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doi = "10.1007/s00125-005-0011-8",

language = "English (US)",

volume = "48",

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T1 - D6S265*15 marks a DRB1*15, DQB1*0602 haplotype associated with attenuated protection from type 1 diabetes mellitus

AU - Valdes, A. M.

AU - Thomson, G.

AU - Graham, J.

AU - Zarghami, M.

AU - McNeney, B.

AU - Kockum, I.

AU - Smith, A.

AU - Lathrop, M.

AU - Steenkiste, A. R.

AU - Dorman, J. S.

AU - Noble, J. A.

AU - Hansen, J. A.

AU - Pugliese, A.

AU - Lernmark, Å

N1 - Funding Information: Acknowledgements This work was supported by grants from the National Institutes of Health (NIH AI-49213 supporting G. Thomson, A. M. Valdes, Å. Lernmark, J. A. Hansen, A. Pugliese, J. S. Dorman, A. R. Steenkiste, A. Smith) and grants DK-26910 and DK-53004 to Å. Lernmark. It was also supported by the American Diabetes Association (grant to A. Pugliese) and the Juvenile Diabetes Research Foundation (grant to Å. Lernmark).

PY - 2005/12

Y1 - 2005/12

N2 - 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.

AB - 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.

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KW - HLA-DQ antigens

KW - IDDM

KW - Type 1 diabetes mellitus

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