PMID- 17661910
OWN - NLM
STAT- MEDLINE
DCOM- 20071012
LR  - 20161124
IS  - 0001-2815 (Print)
IS  - 0001-2815 (Linking)
VI  - 70
IP  - 3
DP  - 2007 Sep
TI  - Analysis of BTNL2 genetic polymorphisms in British and Dutch patients with 
      sarcoidosis.
PG  - 219-27
AB  - Sarcoidosis is a heterogeneous disorder, both phenotypically and genetically. Two 
      independent studies have recently shown that a functional polymorphism within 
      butyrophilin-like 2 (BTNL2) gene predisposes to sarcoidosis independently of the 
      human leukocyte antigen (HLA)-DRB1 alleles. However, in both studies, data 
      analysis was not stratified by Lofgren's syndrome, a clinically and genetically 
      distinct sarcoidosis subset. BTNL2, potentially encoding an immune coreceptor, is 
      adjacent and in linkage disequilibrium (LD) with HLA-DRB1. We investigated six 
      BTNL2 variants, including the functional rs2076530 (G > A), as well as HLA-DRB1 
      alleles, by sequence-specific primers-polymerase chain reaction, in 288 patients 
      and 446 controls from two European countries. In the patient group as a whole, 
      the HLA-DRB1*14 [odds ratio (OR) = 3.1, P(c) = 0.0003], DRB1*12 (OR = 2.5, P(c) = 
      0.003), and BTNL2 rs2076530 A allele (OR = 1.49, P(c) = 0.002) were all 
      associated with disease susceptibility. However, after exclusion of patients 
      presenting with Lofgren's syndrome and after adjusting for HLA-DRB1 alleles, the 
      association between BTNL2 rs2076530 A and disease disappeared (P = 0.23). By 
      contrast, both HLA-DRB1*14 and DRB1*12 remained strongly significant (OR = 3.60, 
      P < 0.0001 and OR = 3.03, P = 0.003, respectively). BTNL2 haplotype 4, tagged by 
      the rs2076530 G allele, also remained associated with non-Lofgren sarcoidosis 
      after adjusting for HLA-DRB1 alleles (OR 0.37, P = 0.016). In summary, 
      HLA-DRB1*14, DRB1*12, and BTNL2 haplotype 4--but not rs2076530 A--are associated 
      with non-Lofgren sarcoidosis. However, the tight LD across the HLA complex makes 
      it difficult to identify the precise location of the susceptibility locus/i. 
      Larger sample sets from different ethnic groups, finer mapping, and more robust 
      LD analyses across the HLA region are needed.
FAU - Spagnolo, P
AU  - Spagnolo P
AD  - Clinical Genomic Group, National Heart and Lung Institute, Department of 
      Occupational and Environmental Medicine, Imperial College, 1B Manresa Road, 
      London, UK. P.Spagnolo@imperial.ac.uk
FAU - Sato, H
AU  - Sato H
FAU - Grutters, J C
AU  - Grutters JC
FAU - Renzoni, E A
AU  - Renzoni EA
FAU - Marshall, S E
AU  - Marshall SE
FAU - Ruven, H J T
AU  - Ruven HJ
FAU - Wells, A U
AU  - Wells AU
FAU - Tzouvelekis, A
AU  - Tzouvelekis A
FAU - van Moorsel, C H M
AU  - van Moorsel CH
FAU - van den Bosch, J M M
AU  - van den Bosch JM
FAU - du Bois, R M
AU  - du Bois RM
FAU - Welsh, K I
AU  - Welsh KI
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Tissue Antigens
JT  - Tissue antigens
JID - 0331072
RN  - 0 (BTNL2 protein, human)
RN  - 0 (Butyrophilins)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (Membrane Glycoproteins)
SB  - IM
MH  - Butyrophilins
MH  - *Genetic Predisposition to Disease
MH  - HLA-DR Antigens/genetics
MH  - HLA-DRB1 Chains
MH  - Humans
MH  - Membrane Glycoproteins/*genetics
MH  - Netherlands
MH  - *Polymorphism, Single Nucleotide
MH  - Sarcoidosis/*genetics
MH  - United Kingdom
EDAT- 2007/07/31 09:00
MHDA- 2007/10/13 09:00
CRDT- 2007/07/31 09:00
PHST- 2007/07/31 09:00 [pubmed]
PHST- 2007/10/13 09:00 [medline]
PHST- 2007/07/31 09:00 [entrez]
AID - TAN879 [pii]
AID - 10.1111/j.1399-0039.2007.00879.x [doi]
PST - ppublish
SO  - Tissue Antigens. 2007 Sep;70(3):219-27. doi: 10.1111/j.1399-0039.2007.00879.x.