Imperial College London
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Dr Shivani Misra

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Clinical Senior Lecturer in Diabetes and Endocrinology
 
 
 
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Contact

 

s.misra

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Thomas:2021:10.1007/s00125-021-05513-4,
author = {Thomas, NJ and Dennis, JM and Sharp, SA and Kaur, A and Misra, S and Walkey, HC and Johnston, DG and Oliver, NS and Hagopian, WA and Weedon, MN and Patel, KA and Oram, RA},
doi = {10.1007/s00125-021-05513-4},
journal = {Diabetologia},
pages = {2258--2265},
title = {DR15-DQ6 remains dominantly protective against type 1 diabetes throughout the first five decades of life},
url = {http://dx.doi.org/10.1007/s00125-021-05513-4},
volume = {64},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Aims/hypothesisAmong white European children developing type 1 diabetes, the otherwise common HLA haplotype DR15-DQ6 is rare, and highly protective. Adult-onset type 1 diabetes is now known to represent more overall cases than childhood onset, but it is not known whether DR15-DQ6 is protective in older-adult-onset type 1 diabetes. We sought to quantify DR15-DQ6 protection against type 1 diabetes as age of onset increased.MethodsIn two independent cohorts we assessed the proportion of type 1 diabetes cases presenting through the first 50 years of life with DR15-DQ6, compared with population controls. In the After Diabetes Diagnosis Research Support System-2 (ADDRESS-2) cohort (n = 1458) clinician-diagnosed type 1 diabetes was confirmed by positivity for one or more islet-specific autoantibodies. In UK Biobank (n = 2502), we estimated type 1 diabetes incidence rates relative to baseline HLA risk for each HLA group using Poisson regression. Analyses were restricted to white Europeans and were performed in three groups according to age at type 1 diabetes onset: 0–18 years, 19–30 years and 31–50 years.ResultsDR15-DQ6 was protective against type 1 diabetes through to age 50 years (OR < 1 for each age group, all p < 0.001). The following ORs for type 1 diabetes, relative to a neutral HLA genotype, were observed in ADDRESS-2: age 5–18 years OR 0.16 (95% CI 0.08, 0.31); age 19–30 years OR 0.10 (0.04, 0.23); and age 31–50 years OR 0.37 (0.21, 0.68). DR15-DQ6 also remained highly protective at all ages in UK Biobank. Without DR15-DQ6, the presence of major type 1 diabetes high-risk haplotype (either DR3-DQ2 or DR4-DQ8) was associated with increased risk of type 1 diabetes.Conclusions/interpretationHLA DR15-DQ6 confers dominant protection from type 1 diabetes across the first five decades of life.
AU  - Thomas,NJ
AU  - Dennis,JM
AU  - Sharp,SA
AU  - Kaur,A
AU  - Misra,S
AU  - Walkey,HC
AU  - Johnston,DG
AU  - Oliver,NS
AU  - Hagopian,WA
AU  - Weedon,MN
AU  - Patel,KA
AU  - Oram,RA
DO  - 10.1007/s00125-021-05513-4
EP  - 2265
PY  - 2021///
SN  - 0012-186X
SP  - 2258
TI  - DR15-DQ6 remains dominantly protective against type 1 diabetes throughout the first five decades of life
T2  - Diabetologia
UR  - http://dx.doi.org/10.1007/s00125-021-05513-4
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000673195500002&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://link.springer.com/article/10.1007/s00125-021-05513-4
UR  - http://hdl.handle.net/10044/1/95106
VL  - 64
ER  -
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