PMID- 16698434
OWN - NLM
STAT- MEDLINE
DCOM- 20060829
LR  - 20221207
IS  - 0198-8859 (Print)
IS  - 0198-8859 (Linking)
VI  - 67
IP  - 1-2
DP  - 2006 Jan-Feb
TI  - Disease relevant HLA class II alleles isolated by genotypic, haplotypic, and 
      sequence analysis in North American Caucasians with pemphigus vulgaris.
PG  - 125-39
AB  - Early studies of genetic susceptibility to pemphigus vulgaris (PV) showed 
      associations between human leukocyte antigen (HLA) DR4 and DR6 and disease. The 
      emergence of DNA sequencing techniques has implicated numerous DRB1 and DQB1 loci 
      in various populations, leading to confusion regarding which exact alleles confer 
      susceptibility. The strong linkage disequilibrium among DR and DQ HLA alleles 
      further complicates the investigation of the true susceptibility loci. In this 
      study, we report genotyping data for the largest sampling of North American 
      Caucasian non-Jewish and Ashkenazi Jewish PV patients studied to date and compare 
      our data with other population studies. To pinpoint true susceptibility, alleles 
      among overrepresented sequences, we applied a step-wise reductionist analysis 
      through (1) determination of the degree of linkage disequilibrium (LD) between 
      purportedly associated alleles, (2) haplotype frequencies comparisons, and (3) 
      primary sequence comparisons of disease-associated versus non-disease-associated 
      alleles to identify crucial differences in amino acid residues in putative 
      peptide binding pockets. Collectively, our data provide extended support for the 
      hypothesis that the HLA associations in Caucasian PV patients map to DRB1*0402 
      and DQB1*0503 alone. Further structure-function studies will be required to 
      define the exact mechanisms of HLA-mediated control of susceptibility and 
      resistance to disease.
FAU - Lee, Erica
AU  - Lee E
AD  - Department of Dermatology, Weill Medical College of Cornell University, New York, 
      NY, USA.
FAU - Lendas, Katherine A
AU  - Lendas KA
FAU - Chow, Selwyn
AU  - Chow S
FAU - Pirani, Yasmin
AU  - Pirani Y
FAU - Gordon, Derek
AU  - Gordon D
FAU - Dionisio, Robert
AU  - Dionisio R
FAU - Nguyen, Daniela
AU  - Nguyen D
FAU - Spizuoco, Amy
AU  - Spizuoco A
FAU - Fotino, Marilena
AU  - Fotino M
FAU - Zhang, Yun
AU  - Zhang Y
FAU - Sinha, Animesh A
AU  - Sinha AA
LA  - eng
GR  - K01-HG00055/HG/NHGRI NIH HHS/United States
GR  - MH44292/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20051104
PL  - United States
TA  - Hum Immunol
JT  - Human immunology
JID - 8010936
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Alleles
MH  - Female
MH  - Gene Frequency
MH  - *Genes, MHC Class II
MH  - Genetic Predisposition to Disease
MH  - Genotype
MH  - HLA Antigens/*genetics
MH  - Haplotypes
MH  - Humans
MH  - Jews/genetics
MH  - Linkage Disequilibrium
MH  - Male
MH  - Middle Aged
MH  - Molecular Epidemiology
MH  - Pemphigus/*epidemiology/*genetics
MH  - Polymorphism, Genetic
MH  - Sequence Analysis, DNA
MH  - United States/epidemiology/ethnology
MH  - White People/*genetics
EDAT- 2006/05/16 09:00
MHDA- 2006/08/30 09:00
CRDT- 2006/05/16 09:00
PHST- 2005/05/17 00:00 [received]
PHST- 2006/05/16 09:00 [pubmed]
PHST- 2006/08/30 09:00 [medline]
PHST- 2006/05/16 09:00 [entrez]
AID - S0198-8859(05)00423-4 [pii]
AID - 10.1016/j.humimm.2005.09.003 [doi]
PST - ppublish
SO  - Hum Immunol. 2006 Jan-Feb;67(1-2):125-39. doi: 10.1016/j.humimm.2005.09.003. Epub 
      2005 Nov 4.