PMID- 14641545
OWN - NLM
STAT- MEDLINE
DCOM- 20040722
LR  - 20191108
IS  - 0960-7420 (Print)
IS  - 0960-7420 (Linking)
VI  - 30
IP  - 5
DP  - 2003 Oct
TI  - Geographic patterns of functional categories of HLA-DRB1 alleles: a new approach 
      to analyse associations between HLA-DRB1 and disease.
PG  - 361-74
AB  - Because specific amino acids found within the peptide-binding cleft of human 
      leukocyte antigen (HLA) molecules have been implicated in HLA/disease 
      associations, an approach which consists in grouping the alleles according to 
      their functional properties at the protein level may enable us to better 
      understand HLA associations than the conventional allelic classification. In this 
      study, we applied this methodology to investigate the associations between 
      HLA-DRB1 and rheumatoid arthritis. The alleles were first classified into seven 
      functional categories [restrictive supertype patterns (RSPs)], among which three 
      were known to be significantly associated with susceptibility (one category) or 
      resistance (two categories) to rheumatoid arthritis. The frequencies of these 
      categories were then estimated in 104 population samples previously tested for 
      HLA-DRB1, and their variability was analysed spatially on a worldwide scale by 
      applying an original methodology for detecting discontinuities in geographically 
      patterned data. RSP frequencies were also compared to known values of rheumatoid 
      arthritis prevalence in some populations. The results indicated that the three 
      RSP frequency distributions were geographically structured, and that these 
      patterns could generally be explained by the history of human migrations. 
      However, the peculiar pattern observed for RSP 'A' (conferring susceptibility to 
      rheumatoid arthritis) indicated a possible association with some 
      latitude-dependent disease. Furthermore, the very high correlation coefficient 
      found between RSP 'A' frequencies and rheumatoid arthritis prevalence confirmed 
      the significant disease association of this functional category. In contrast, the 
      putative protective effect of the other RSPs ('De' and 'Q') was not detectable at 
      the worldwide level, but may be significant in specific geographic areas. This 
      study shows that population genetic diversity analyses based on a functional 
      grouping of HLA alleles provide an efficient way to explore the mutual influence 
      of HLA genetic variation and disease.
FAU - Gibert, M
AU  - Gibert M
AD  - Universite de la Mediterranee, Marseille Cedex 5, France. 
      morganegibert@netcourrier.com
FAU - Sanchez-Mazas, A
AU  - Sanchez-Mazas A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Immunogenet
JT  - European journal of immunogenetics : official journal of the British Society for 
      Histocompatibility and Immunogenetics
JID - 9106962
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DRB1 Chains)
SB  - IM
MH  - Alleles
MH  - Arthritis, Rheumatoid/epidemiology/genetics
MH  - Data Interpretation, Statistical
MH  - *Genetic Predisposition to Disease
MH  - Geography
MH  - HLA-DR Antigens/*genetics
MH  - HLA-DRB1 Chains
MH  - Humans
EDAT- 2003/12/04 05:00
MHDA- 2004/07/23 05:00
CRDT- 2003/12/04 05:00
PHST- 2003/12/04 05:00 [pubmed]
PHST- 2004/07/23 05:00 [medline]
PHST- 2003/12/04 05:00 [entrez]
AID - 418 [pii]
AID - 10.1046/j.1365-2370.2003.00418.x [doi]
PST - ppublish
SO  - Eur J Immunogenet. 2003 Oct;30(5):361-74. doi: 10.1046/j.1365-2370.2003.00418.x.