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; Åke Lernmark; Swedish Childhood Study Group, Diabetes Incidence in Sweden Study Group, Type 1 Diabetes Component of the 13th International Histocompatibility Working Group

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, Åke Lernmark, Swedish Childhood Study Group, Diabetes Incidence in Sweden Study Group, Type 1 Diabetes Component of the 13th International Histocompatibility Working Group

University of Washington, Seattle

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

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.
Electronic Supplementary Material: Supplementary material is available for this article at http://dx.doi.org/10.1007/s00125-005-0011-8

Original language	English
Pages (from-to)	2540-2543
Journal	Diabetologia
Volume	48
Issue number	12
DOIs	https://doi.org/10.1007/s00125-005-0011-8
Publication status	Published - 2005
Externally published	Yes

Subject classification (UKÄ)

Endocrinology and Diabetes

Free keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1007/s00125-005-0011-8

Cite this

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., & Swedish Childhood Study Group, Diabetes Incidence in Sweden Study Group, Type 1 Diabetes Component of the 13th International Histocompatibility Working Group (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

@article{a486139d1966452f88d88d3e6c9673f9,

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. Electronic Supplementary Material: Supplementary material is available for this article at http://dx.doi.org/10.1007/s00125-005-0011-8",

keywords = "D6S265, DQB1*0602, 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}ke Lernmark and {Swedish Childhood Study Group, Diabetes Incidence in Sweden Study Group, Type 1 Diabetes Component of the 13th International Histocompatibility Working Group}",

year = "2005",

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

language = "English",

volume = "48",

pages = "2540--2543",

journal = "Diabetologia",

issn = "1432-0428",

publisher = "Springer",

number = "12",

}

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 & Swedish Childhood Study Group, Diabetes Incidence in Sweden Study Group, Type 1 Diabetes Component of the 13th International Histocompatibility Working Group 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

TY - JOUR

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, Åke

AU - Swedish Childhood Study Group, Diabetes Incidence in Sweden Study Group, Type 1 Diabetes Component of the 13th International Histocompatibility Working Group

PY - 2005

Y1 - 2005

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. Electronic Supplementary Material: Supplementary material is available for this article at http://dx.doi.org/10.1007/s00125-005-0011-8

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. Electronic Supplementary Material: Supplementary material is available for this article at http://dx.doi.org/10.1007/s00125-005-0011-8

KW - D6S265

KW - DQB10602

KW - HLA-DQ antigens

KW - IDDM

KW - Type 1 diabetes mellitus

U2 - 10.1007/s00125-005-0011-8

DO - 10.1007/s00125-005-0011-8

M3 - Letter

SN - 1432-0428

VL - 48

SP - 2540

EP - 2543

JO - Diabetologia

JF - Diabetologia

IS - 12

ER -