PMID- 18486765
OWN - NLM
STAT- MEDLINE
DCOM- 20080721
LR  - 20211020
IS  - 0198-8859 (Print)
IS  - 0198-8859 (Linking)
VI  - 69
IP  - 4-5
DP  - 2008 Apr-May
TI  - Type 1 diabetes risk for human leukocyte antigen (HLA)-DR3 haplotypes depends on 
      genotypic context: association of DPB1 and HLA class I loci among DR3- and 
      DR4-matched Italian patients and controls.
PG  - 291-300
LID - 10.1016/j.humimm.2008.02.003 [doi]
AB  - Patients with high-risk human leukocyte antigen (HLA)-DR-DQ genotypes for type 1 
      diabetes (T1D) were compared with HLA-matched controls to evaluate T1D risk for 
      other HLA loci, including HLA-A, -B, -Cw, and DPB1. Patients (n = 133) with 
      high-risk genotypes (DR3/DR3, DR3/DR4, DR4/DR4) were selected from the Lazio 
      (Rome) region of Italy. Screening of more than 9000 patients from the Lazio 
      region and northern Italy yielded 162 controls with high-T1D-risk haplotypes. 
      Although the overall distributions did not differ significantly, allele frequency 
      differences were discovered between the controls from Lazio and controls from 
      northern Italy for some alleles previously determined to affect T1D risk, such as 
      A*3002, DPB1*0301, and DPB1*0402. Therefore, Lazio patient data were compared 
      both with the Lazio subset of controls (n = 53) and with the entire group of 
      controls for association analyses. Significant allele frequency differences 
      between patients and DR-DQ-matched controls existed for specific alleles at all 
      loci. Data for the DR3/DR3 subset of patients and controls demonstrated an 
      increase of Cw*0702 in patients. Compared with controls, reduced patient 
      frequencies were seen for several alleles, including A*0101, B*0801, and Cw*0701, 
      all on the highly conserved, extended DR3 haplotype known as 8.1 in DR3/DR3, but 
      not DR3/DR4, subgroup. DPB1*0101, often reported on 8.1 haplotypes, was also less 
      frequent in DR3/DR3 patients than controls. Analysis of family-based data from 
      the HBDI repository was consistent with the observed results from the Italian 
      patients, indicating the presence of a T1D-protective locus at or near A*0101 and 
      a second T1D-protective locus at or near DPB1*0101. These data indicate that T1D 
      risk conferred by the 8.1 haplotype is genotype dependent.
FAU - Noble, Janelle A
AU  - Noble JA
AD  - Childrens Hospital Oakland Research Institute, Oakland, CA, USA. jnoble@chori.org
FAU - Martin, Adelle
AU  - Martin A
FAU - Valdes, Ana M
AU  - Valdes AM
FAU - Lane, Julie A
AU  - Lane JA
FAU - Galgani, Andrea
AU  - Galgani A
FAU - Petrone, Antonio
AU  - Petrone A
FAU - Lorini, Renata
AU  - Lorini R
FAU - Pozzilli, Paolo
AU  - Pozzilli P
FAU - Buzzetti, Raffaella
AU  - Buzzetti R
FAU - Erlich, Henry A
AU  - Erlich HA
LA  - eng
GR  - R01 DK061722/DK/NIDDK NIH HHS/United States
GR  - R01 DK061722-01A1/DK/NIDDK NIH HHS/United States
GR  - R56 DK061722/DK/NIDDK NIH HHS/United States
GR  - DK61722/DK/NIDDK NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080326
PL  - United States
TA  - Hum Immunol
JT  - Human immunology
JID - 8010936
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-A*01:01 antigen)
RN  - 0 (HLA-A1 Antigen)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-B*08:01 antigen)
RN  - 0 (HLA-B8 Antigen)
RN  - 0 (HLA-DP Antigens)
RN  - 0 (HLA-DP beta-Chains)
RN  - 0 (HLA-DPB1 antigen)
RN  - 0 (HLA-DR3 Antigen)
RN  - 0 (HLA-DR4 Antigen)
SB  - IM
MH  - Case-Control Studies
MH  - Diabetes Mellitus, Type 1/epidemiology/*genetics
MH  - Gene Frequency
MH  - Genetic Predisposition to Disease
MH  - HLA-A Antigens/*genetics
MH  - HLA-A1 Antigen
MH  - HLA-B Antigens/genetics
MH  - HLA-B8 Antigen
MH  - HLA-DP Antigens/*genetics
MH  - HLA-DP beta-Chains
MH  - HLA-DR3 Antigen/*genetics
MH  - HLA-DR4 Antigen/*genetics
MH  - *Haplotypes
MH  - Heterozygote
MH  - Homozygote
MH  - Humans
MH  - Infant, Newborn
MH  - Italy/epidemiology
PMC - PMC2505335
MID - NIHMS53345
EDAT- 2008/05/20 09:00
MHDA- 2008/07/22 09:00
PMCR- 2008/08/11
CRDT- 2008/05/20 09:00
PHST- 2007/08/23 00:00 [received]
PHST- 2008/02/14 00:00 [revised]
PHST- 2008/02/21 00:00 [accepted]
PHST- 2008/05/20 09:00 [pubmed]
PHST- 2008/07/22 09:00 [medline]
PHST- 2008/05/20 09:00 [entrez]
PHST- 2008/08/11 00:00 [pmc-release]
AID - S0198-8859(08)00039-6 [pii]
AID - 10.1016/j.humimm.2008.02.003 [doi]
PST - ppublish
SO  - Hum Immunol. 2008 Apr-May;69(4-5):291-300. doi: 10.1016/j.humimm.2008.02.003. 
      Epub 2008 Mar 26.