WFRF:(Ortqvist Eva)
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Next-Generation Sequencing Reveals That HLA-DRB3, -DRB4, and -DRB5 May Be Associated With Islet Autoantibodies and Risk for Childhood Type 1 Diabetes
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- Ping Zhao, Lue (author)
- Fred Hutchinson Cancer Research Centre, WA 98104 USA
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- Alshiekh, Shehab (author)
- Lund University,Lunds universitet,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Celiac Disease and Diabetes Unit,Lund University Research Groups,Lund University, Sweden
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- Zhao, Michael (author)
- Fred Hutchinson Cancer Research Centre, WA 98104 USA
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- (creator_code:org_t)
- 2016-01-06
- 2016
- English.
- In: Diabetes. - : AMER DIABETES ASSOC. - 0012-1797 .- 1939-327X. ; 65:3, s. 710-718
- Journal article (peer-reviewed)
Abstract
Subject headings
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- The possible contribution of HLA-DRB3, -DRB4, and -DRB5 alleles to type 1 diabetes risk and to insulin autoantibody (IAA), GAD65 (GAD autoantibody [GADA]), IA-2 antigen (IA-2A), or ZnT8 against either of the three amino acid variants R, W, or Q at position 325 (ZnT8RA, ZnT8WA, and ZnT8QA, respectively) at clinical diagnosis is unclear. Next-generation sequencing (NGS) was used to determine all DRB alleles in consecutively diagnosed patients ages 1-18 years with islet autoantibody-positive type 1 diabetes (n = 970) and control subjects (n = 448). DRB3, DRB4, or DRB5 alleles were tested for an association with the risk of DRB1 for autoantibodies, type 1 diabetes, or both. The association between type 1 diabetes and DRB1*03:01:01 was affected by DRB3*01:01:02 and DRB3*02:02:01. These DRB3 alleles were associated positively with GADA but negatively with ZnT8WA, IA-2A, and IAA. The negative association between type 1 diabetes and DRB1*13:01:01 was affected by DRB3*01:01:02 to increase the risk and by DRB3*02:02:01 to maintain a negative association. DRB4*01:03:01 was strongly associated with type 1 diabetes (P = 10(-36)), yet its association was extensively affected by DRB1 alleles from protective (DRB1*04:03:01) to high (DRB1*04:01:01) risk, but its association with DRB1*04:05:01 decreased the risk. HLA-DRB3, -DRB4, and -DRB5 affect type 1 diabetes risk and islet autoantibodies. HLA typing with NGS should prove useful to select participants for prevention or intervention trials.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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- Ping Zhao, Lue
- Alshiekh, Shehab
- Zhao, Michael
- Carlsson, Anneli ...
- Larsson, Helena
- Forsander, Gun
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- Ivarsson, Sten
- Ludvigsson, John ...
- Kockum, Ingrid
- Marcus, Claude
- Persson, Martina
- Samuelsson, Ulf
- Ortqvist, Eva
- Pyo, Chul-Woo
- Nelson, Wyatt C.
- Geraghty, Daniel ...
- Lernmark, Åke
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- Diabetes
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- Lund University
- Karolinska Institutet
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