Advanced

Relative predispositional effects of HLA class II DRB1-DQB1 haplotypes and genotypes on type 1 diabetes: a meta-analysis.

Thomson, G; Valdes, AM; Noble, JA; Kockum, I; Grote, MN; Najman, J; Erlich, HA; Cucca, F; Pugliese, A and Steenkiste, A, et al. (2007) In Tissue Antigens 70(2). p.110-127
Abstract
The direct involvement of the human leukocyte antigen class II DR-DQ genes in type 1 diabetes (T1D) is well established, and these genes display a complex hierarchy of risk effects at the genotype and haplotype levels. We investigated, using data from 38 studies, whether the DR-DQ haplotypes and genotypes show the same relative predispositional effects across populations and ethnic groups. Significant differences in risk within a population were considered, as well as comparisons across populations using the patient/control (P/C) ratio. Within a population, the ratio of the P/C ratios for two different genotypes or haplotypes is a function only of the absolute penetrance values, allowing ranking of risk effects. Categories of consistent... (More)
The direct involvement of the human leukocyte antigen class II DR-DQ genes in type 1 diabetes (T1D) is well established, and these genes display a complex hierarchy of risk effects at the genotype and haplotype levels. We investigated, using data from 38 studies, whether the DR-DQ haplotypes and genotypes show the same relative predispositional effects across populations and ethnic groups. Significant differences in risk within a population were considered, as well as comparisons across populations using the patient/control (P/C) ratio. Within a population, the ratio of the P/C ratios for two different genotypes or haplotypes is a function only of the absolute penetrance values, allowing ranking of risk effects. Categories of consistent predisposing, intermediate ('neutral'), and protective haplotypes were identified and found to correlate with disease prevalence and the marked ethnic differences in DRB1-DQB1 frequencies. Specific effects were identified, for example for predisposing haplotypes, there was a statistically significant and consistent hierarchy for DR4 DQB1*0302s: DRB1*0405 =*0401 =*0402 > *0404 > *0403, with DRB1*0301 DQB1*0200 (DR3) being significantly less predisposing than DRB1*0402 and more than DRB1*0404. The predisposing DRB1*0401 DQB1*0302 haplotype was relatively increased compared with the protective haplotype DRB1*0401 DQB1*0301 in heterozygotes with DR3 compared with heterozygotes with DRB1*0101 DQB1*0501 (DR1). Our results show that meta-analyses and use of the P/C ratio and rankings thereof can be valuable in determining T1D risk factors at the haplotype and amino acid residue levels. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
human leukocyte antigen class II DRB1-DQB1, meta-analysis, type 1 diabetes
in
Tissue Antigens
volume
70
issue
2
pages
110 - 127
publisher
Wiley-Blackwell
external identifiers
  • scopus:34347389454
ISSN
0001-2815
DOI
10.1111/j.1399-0039.2007.00867.x
language
English
LU publication?
yes
id
2a8ea94b-4dc5-46f8-86a9-8dd5e4a882e8 (old id 1140950)
date added to LUP
2008-08-13 15:47:04
date last changed
2017-06-25 04:46:41
@article{2a8ea94b-4dc5-46f8-86a9-8dd5e4a882e8,
  abstract     = {The direct involvement of the human leukocyte antigen class II DR-DQ genes in type 1 diabetes (T1D) is well established, and these genes display a complex hierarchy of risk effects at the genotype and haplotype levels. We investigated, using data from 38 studies, whether the DR-DQ haplotypes and genotypes show the same relative predispositional effects across populations and ethnic groups. Significant differences in risk within a population were considered, as well as comparisons across populations using the patient/control (P/C) ratio. Within a population, the ratio of the P/C ratios for two different genotypes or haplotypes is a function only of the absolute penetrance values, allowing ranking of risk effects. Categories of consistent predisposing, intermediate ('neutral'), and protective haplotypes were identified and found to correlate with disease prevalence and the marked ethnic differences in DRB1-DQB1 frequencies. Specific effects were identified, for example for predisposing haplotypes, there was a statistically significant and consistent hierarchy for DR4 DQB1*0302s: DRB1*0405 =*0401 =*0402 > *0404 > *0403, with DRB1*0301 DQB1*0200 (DR3) being significantly less predisposing than DRB1*0402 and more than DRB1*0404. The predisposing DRB1*0401 DQB1*0302 haplotype was relatively increased compared with the protective haplotype DRB1*0401 DQB1*0301 in heterozygotes with DR3 compared with heterozygotes with DRB1*0101 DQB1*0501 (DR1). Our results show that meta-analyses and use of the P/C ratio and rankings thereof can be valuable in determining T1D risk factors at the haplotype and amino acid residue levels.},
  author       = {Thomson, G and Valdes, AM and Noble, JA and Kockum, I and Grote, MN and Najman, J and Erlich, HA and Cucca, F and Pugliese, A and Steenkiste, A and Dorman, JS and Caillat-Zucman, S and Hermann, R and Ilonen, J and Lambert, AP and Bingley, PJ and Gillespie, KM and Lernmark, Åke and Sanjeevi, CB and Rønningen, KS and Undlien, DE and Thorsby, E},
  issn         = {0001-2815},
  keyword      = {human leukocyte antigen class II DRB1-DQB1,meta-analysis,type 1 diabetes},
  language     = {eng},
  number       = {2},
  pages        = {110--127},
  publisher    = {Wiley-Blackwell},
  series       = {Tissue Antigens},
  title        = {Relative predispositional effects of HLA class II DRB1-DQB1 haplotypes and genotypes on type 1 diabetes: a meta-analysis.},
  url          = {http://dx.doi.org/10.1111/j.1399-0039.2007.00867.x},
  volume       = {70},
  year         = {2007},
}